There is increasing evidence that dynamic changes to chromatin, chromosomes and nuclear architecture are regulated by RNA signalling. Although the precise molecular mechanisms are not well understood, they appear to involve the differential recruitment of a hierarchy of generic chromatin modifying complexes and DNA methyltransferases to specific loci by RNAs during differentiation and development. A significant fraction of the genome-wide transcription of non-protein coding RNAs may be involved in this process, comprising a previously hidden layer of intermediary genetic information that (...) underpins developmental ontogeny and the differences between species, ecotypes and individuals. It is also evident that RNA editing is a primary means by which hardwired genetic information in animals can be altered by environmental signals, especially in the brain, indicating a dynamic RNA-mediated interplay between the transcriptome, the environment and the epigenome. Moreover, RNA-directed regulatory processes may also transfer epigenetic information not only within cells but also between cells and organ systems, as well as across generations. (shrink)

Drawing on research in posthumanism, science and technology studies and biosemiotics, this essay analyses the challenges epigenetic processes pose for our understanding of embodied subjectivity. It uses the work of Charles Sanders Peirce to argue that epigenetic processes are indexical in their patterned logic, that they are meaning-making processes and that, consequently, they can be conceived as a form of attention. To conceive of bodies as paying attention through epigenetic processes is to rupture (...) the distinction between matter and meaning that governs many philosophical categories. This in turn invites us to recalibrate our conception of the relationship between self, body and world. (shrink)

The interview is a follow-up from Samantha Frost’s article, ‘The Attentive Body’, in Body & Society 26. Tomoko Tamari invites Frost to explore her interest in ‘biocultural creatures’, with its focus on ‘bodies’ responsive self-transformation’ in epigenetic processes, and unfolds Peirce’s account of the index for understanding meaning-making in biological processes. Tamari also introduces Katherine Hayles’s notion of ‘cognitive nonconscious’ to raise the question of the possible theoretical and mechanical similarities/discrepancies between epigenetic processes in organisms (...) and the meaning-making process in computational systems. Drawing on Jacob von Uexkull’s notion of ‘umwelt’ and introducing Yoshimi Kawade’s remarks on a living being’s subjective orientation in environments, a further question about ‘intention’ and ‘subjectivity’ enables Frost to further unpack her notion of ‘the attentive self’ and discuss its relation to ‘intentionality’ and ‘referentiality’ in epigenetic processes. Finally, Samantha Frost mentions her current projects on the connection between ‘attention-as-responsive-self-transformation’ and ‘mode-of-living-as-form-of-life’. (shrink)

Silencing of tumor suppressor genes (TSGs), by DNA methylation, is well known in adult cancers. However, based on the “stem cell” theory of tumorigenesis, the early epigenetic events arising in malignant precursors remain unknown. A recent report1 demonstrates that, while pluripotent embryonic stem cells lack DNA methylation and possess a “bivalent” pattern of activating and repressive histone marks in numerous TSGs, analogous multipotent malignant cells derived from germ cell tumors (embryonic carcinoma cells) gain additional silencing modifications to those same (...) genes. These results suggest a possible mechanism by which aberrant differentiation, mediated by histone and DNA methylation, instigates tumor progression. BioEssays 29:842–845, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Four sequential, sub-processes are identified as the fundamental steps in the processing of signals by big-brained animals. These are, Detection of the signal, its Representation in correlated sensory brain structure, the Interpretation of the signal in another part of the brain and the Expression of the receiver’s response. We label this four-step spatiotemporal process DRIE. We support the view that when the context within which such signals are produced and received is relatively constant, the DRIE process can be ultimately (...) assimilated into the genome, with the Interpretation sub-phase is markedly decreased in duration as speed and efficiency are maximized. With frequent repetition and learning, an analogous result can be attained epigenetically as exemplified in human word and text recognition, allowing tasks critical to primate social function to be accomplished with rapidity and accuracy. (shrink)

Bourdieu suggested that the habitus contains the ‘genetic information’ which both allows and disposes successive generations to reproduce the world they inherit from their parents’ generation. While his writings on habitus are concerned with embodied dispositions, biological processes are not a feature of the practical reason of habitus. Recent critiques of the separate worlds of biology and culture, and the rise in epigenetics, provide new opportunities for expanding theoretical concepts like habitus. Using obesity science as a case study we (...) attempt to conceptualise the enfolding of biological and social processes (via a Deleuzian metaphor) to develop a concept of biohabitus – reconfiguring how social and biological environments interact across the life course, and may be transmitted and transformed intergenerationally. In conclusion we suggest that the enfolding and reproduction of social life that Bourdieu articulated as habitus is a useful theoretical frame that can be enhanced to critically develop epigenetic understandings of obesity, and vice versa. (shrink)

This chapter offers a brief review of theories on mirror neuron development, highlighting different models. These models focus on either the role of genetic mechanisms or the contributions of experience and of learning processes in shaping the brain circuits involved in action–perception coupling. As an alternative, the chapter proposes an epigenetic model for mirror neuron development, explaining how such a model can help to elucidate, within a unifying explanatory framework, the emergence, diversity, and functional reuse of mirror neurons. (...) Lastly, a related evolutionary scenario is sketched in which epigenetic regulation, genetic assimilation/the Baldwin effect, and niche construction play crucial roles in mirror neuron evolution. (shrink)

Recent findings in epigenetics have been attracting much attention from social scientists and bioethicists because they reveal the molecular mechanisms by which exposure to socioenvironmental factors, such as pollutants and social adversity, can influence the expression of genes throughout life. Most surprisingly, some epigenetic modifications may also be heritable via germ cells across generations. Epigenetics may be the missing molecular evidence of the importance of using preventive strategies at the policy level to reduce the incidence and prevalence of common (...) diseases. But while this “policy translation” of epigenetics introduces new arguments in favor of public health strategies and policy-making, a more “clinical translation” of epigenetics is also emerging. It focuses on the biochemical mechanisms and epigenetic variants at the origin of disease, leading to novel biomedical means of assessing epigenetic susceptibility and reversing detrimental epigenetic variants. In this paper, we argue that the impetus to create new biomedical interventions to manipulate and reverse epigenetic variants is likely to garner more attention than effective social and public health interventions and therefore also to garner a greater share of limited public resources. This is likely to happen because of the current biopolitical context in which scientific findings are translated. This contemporary neoliberal “regime of truth,” to use a term from Michel Foucault, greatly influences the ways in which knowledge is being interpreted and implemented. Building on sociologist Thomas Lemke's Foucauldian “analytics of biopolitics” and on literature from the field of science and technology studies, we present two sociological trends that may impede the policy translation of epigenetics: molecularization and biomedicalization. These trends, we argue, are likely to favor the clinical translation of epigenetics—in other words, the development of new clinical tools fostering what has been called “personalized” or “precision” medicine. In addition, we argue that an overemphasized clinical translation of epigenetics may further reinforce this biopolitical landscape through four processes closely related to neoliberal pathways of thinking: the internalization and isolation of socioenvironmental determinants of health and increased opportunities for commodification and technologicalization of health care interventions. (shrink)

Transcriptome sequencing has identified more than a thousand potentially imprinted genes in the mouse brain. This comes as a revelation to someone who cut his teeth on the identification of imprinted genes when only a handful was known. Genomic imprinting, an epigenetic mechanism that determines expression of alleles according to sex of transmitting parent, was discovered over 25 years ago in mice but remains an enigmatic phenomenon. Why do these genes disobey the normal Mendelian logic of inheritance, do they (...) function in specific processes, and how is their imprinting conferred? Next generation sequencing technologies are providing an unprecedented opportunity to survey the whole genome for imprinted genes and are beginning to reveal that imprinting may be more pervasive than we had come to believe. Such advances should lay the foundation for a definitive account of imprinting, but may also challenge accepted views on what it means to be imprinted.Editor's suggested further reading in BioEssays RNA as the substrate for epigenome‐environment interactions Abstract. (shrink)

Rejuvenation of cells by reprogramming toward the pluripotent state raises increasing attention. In fact, generation of induced pluripotent stem cells (iPSCs) completely reverses age‐associated molecular features, including elongation of telomeres, resetting of epigenetic clocks and age‐associated transcriptomic changes, and even evasion of replicative senescence. However, reprogramming into iPSCs also entails complete de‐differentiation with loss of cellular identity, as well as the risk of teratoma formation in anti‐ageing treatment paradigms. Recent studies indicate that partial reprogramming by limited exposure to reprogramming (...) factors can reset epigenetic ageing clocks while maintaining cellular identity. So far, there is no commonly accepted definition of partial reprogramming, which is alternatively called interrupted reprogramming, and it remains to be elucidated how the process can be controlled and if it resembles a stable intermediate state. In this review, we discuss if the rejuvenation program can be uncoupled from the pluripotency program or if ageing and cell fate determination are inextricably linked. Alternative rejuvenation approaches with reprogramming into a pluripotent state, partial reprogramming, transdifferentiation, and the possibility of selective resetting of cellular clocks are also discussed. (shrink)

Epigenetics is currently one of the fastest-growing fields in the sciences. Epigenetic information not only controls DNA expression but links genetic factors with the environmental experiences that influence the traits and characteristics of an individual. What we eat, where we work, and how we live affects not only the activity of our genes but that of our offspring as well. This discovery has imposed a revolutionary theoretical shift on modern biology, especially on evolutionary theory. It has helped to uncover (...) the developmental processes leading to cancer, obesity, schizophrenia, alcoholism, and aging, and to facilitate associated medial applications such as stem cell therapy and cloning. Above the Gene, Beyond Biology explores how biologists in this booming field investigate and explain living systems. Jan Baedke offers the first comprehensive philosophical discussion of epigenetic concepts, explanations, and methodologies so that we can better understand this "epigenetic turn" in the life sciences from a philosophical perspective. (shrink)

The argument that heritable epigenetic change plays a distinct role in evolution would be strengthened through recognition that it is what bootstrapped the origin and early evolution of life, and that, like behavioral and symbolic change, it is non-Darwinian. The mathematics of natural selection, a population-level process, is limited to replication with negligible individual-level change that uses a self-assembly code.

Genetic and early environmental factors are interwoven in the etiology of Borderline Personality Disorder (BPD). Epigenetic mechanisms offer the molecular machinery to adapt to environmental conditions. There are gaps in the knowledge about how epigenetic mechanisms are involved in the effects of early affective environment, development of BPD, and psychotherapy response. We reviewed the available evidence of the effects of psychotherapy on changes in DNA methylation and conducted a pilot study in a sample of 11 female adolescents diagnosed (...) with BPD, exploring for changes in peripheral DNA methylation of FKBP5 gene, which encodes for a stress response protein, in relation to psychotherapy, on symptomatology and underlying psychological processes. For this purpose, measures of early trauma, borderline and depressive symptoms, psychotherapy outcome, mentalization, and emotional regulation were studied. A reduction in the average FKBP5 methylation levels was observed over time. Additionally, the decrease in FKBP5 methylation observed occurred only in those individuals who had early trauma and responded to psychotherapy. The results suggest an effect of psychotherapy on epigenetic mechanisms associated with the stress response. The finding that epigenetic changes were only observed in patients with early trauma suggests a specific molecular mechanism of recovery. The results should be taken with caution given the small sample size. Also, further research is needed to adjust for confounding factors and include endocrinological markers and therapeutic process variables. (shrink)

This article compares two different bodies of theories concerning the role of the genome in life processes. The first group of theories can be indicated as referring to the gene-centric paradigm. Dominated by an informational myth and a mechanistic Cartesian body/mind and form/substance dualism, this considers the genome as an ensemble of discrete units of information governing human body and behavior, and remains hegemonic in life sciences and in the public imagination. The second body of theories employs the principle (...) of the extraordinary plasticity of the (body-)organism and emphasizes the value of the (body-)organism-environment mutual interchange, known as ‘the epigenetic approach’. This approach is outlined, showing a gradual, paradigmatic shift from the genecentric towards an epigenetic approach can be observed in the ‘scientific landscape’ over the last 20 years. The article concludes by formulating the argument that this ‘epigenetic turn’ in life sciences has some important implication for renewing epistemological basis of social sciences. (shrink)

Epigenetic modifications, such as DNA methylation and post‐translation modifications of histones, have been shown to play an important role in chromatin structure, promoter activity, and cellular reprogramming. Large protein complexes, such as Polycomb and trithorax, often harbor multiple activities which affect histone tail modification. Nevertheless, the mechanisms underlying the deposition of these marks, their propagation during cell replication, and the alteration on their distribution during transformation still require further study. Here we review recent data on those processes in (...) both normal and cancer cells, and we propose that the unscheduled expression of oncogenic transcription factors causes reprogramming of normal cells into cancer stem cells. (shrink)

In 1956, in his Principles of Embryology, Conrad Hal Waddington explained that the word “epigenetics” should be used to translate and update Wilhelm Roux’ German notion of “Entwicklungsmechanik” to qualify the studies focusing on the mechanisms of development. When Waddington mentioned it in 1956, the notion of epigenetics was not yet popular, as it would become from the 1980s. However, Waddington referred first to the notion in the late 1930s. While his late allusion clearly reveals that Waddington readily associated the (...) notion of epigenetics with the developmental process, in the contemporary uses of the notion this developmental connotation seems to have disappeared. The advent and success of molecular biology have probably contributed to focusing biologists’ attention on the “genetic” or the “non-genetic” over the “developmental”. In the present paper, I first examine the links that exist, in Waddington’s work, between the classical notion of epigenesis in embryology and those of epigenetics that Waddington proposed to connect, and even synthesize, data both from embryology and genetics. Second, I show that Waddington’s own view of epigenetics has changed over time and I analyze how these changes appear through his many representations of the relationships between genetic signals and developmental processes. (shrink)

This article develops a biosemiotic ´hyper-narrative model´ for the purposes of investigating emergent motor behaviors. It proposes to understand such behaviors in terms of the following associations: the organization of information acquired from the environment, focusing on narrative; the organizational dynamics of epigenetic mechanisms that underly the neural processes facilitating the processing of information; and the evolution of emergent motor behaviors that enable the informational acquisition. The article describes and explains these associations as part of a multi-ordered and (...) multi-causal generative principle of biological phenotype emergence that supersedes the theory of the arbitrary coding of life. Preceeding from narrative’s operations in a biological dimension, the article presents scientific research dealing with the associations of action-oriented organization of narrative information and underlying psychological and physiological dynamics and depicts the relations with a distributed multi-directional mapping dynamic. The article presents the explanatory implications of such a hyper-narrative dynamic model on an example of emergent motor behaviors – bruxism. Central to this discussion is the exploration of the possible mechanisms of emergence and etiopathogenesis of bruxism, based on its neurobiology. The article takes the perspective that complex systems dynamics themselves with a tendency to narrative form are found not to be underlain merely by arbitrary coded mechanisms but, rather, biological neural networks that render context-dependent bio-informational mapping analogous to that of the narrative possible. (shrink)

A history of colonization inflicts psychological, physical, and structural disadvantages that endure across generations. For an increasing number of Indigenous Australians, environmental epigenetics offers an important explanatory framework that links the social past with the biological present, providing a culturally relevant way of understanding the various intergenerational effects of historical trauma. In this paper, we critically examine the strategic uptake of environmental epigenetics by Indigenous researchers and policy advocates. We focus on the relationship between epigenetic processes and Indigenous (...) views of Country and health—views that locate health not in individual bodies but within relational contexts of Indigenous ontologies that embody interconnected environments of kin/animals/matter/bodies across time and space. This drawing together of Indigenous experience and epigenetic knowledge has strengthened calls for action including state-supported calls for financial reparations. We examine the consequences of this reimagining of disease responsibility in the context of “strategic biological essentialism,” a distinct form of biopolitics that, in this case, incorporates environmental determinism. We conclude that the shaping of the right to protection from biosocial injury is potentially empowering but also has the capacity to conceal forms of governance through claimants’ identification as “damaged,” thus furthering State justification of biopolitical intervention in Indigenous lives. (shrink)

Jablonka & Lamb (J&L) refer only implicitly to aspects of cognitive competence that preceded both evolution of human language and language learning in children. These aspects are important for evolution and development but need to be understood using the design-stance, which the book adopts only for molecular and genetic processes, not for behavioural and symbolic processes. Design-based analyses reveal more routes from genome to behaviour than J&L seem to have considered. This both points to gaps in our understanding (...) of evolution and epigenetic processes and may lead to possible ways of filling the gaps. (shrink)

Since the 1990s, the terms “Lamarckism” and “Lamarckian” have seen a significant resurgence in biological publications. The discovery of new molecular mechanisms have been interpreted as evidence supporting the reality and efficiency of the inheritance of acquired characters, and thus the revival of Lamarckism. The present paper aims at giving a critical evaluation of such interpretations. I argue that two types of arguments allow to draw a clear distinction between the genuine Lamarckian concept of inheritance of acquired characters and transgenerational (...) epigenetic inheritance. The first concerns the explanandum of the processes under consideration: molecular mechanisms of transgenerational epigenetic inheritance are understood as evolved products of natural selection. This means that the kind of inheritance of acquired characters they might be responsible for is an obligatory emergent feature of evolution, whereas traditional Lamarckisms conceived the inheritance of acquired characters as a property inherent in living matter itself. The second argument concerns the explanans of the inheritance of acquired characters: in light of current knowledge, epigenetic mechanisms are not able to drive adaptive evolution by themselves. Emergent Lamarckian phenomena would be possible if and only if individual epigenetic variation allowed the inheritance of acquired characters to be a factor of unlimited change. This implies specific requirements for epigenetic variation, which I explicitly define and expand upon. I then show that given current knowledge, these requirements are not empirically grounded. (shrink)

John Dupré explores recent revolutionary developments in biology and considers their relevance for our understanding of human nature and human society. Epigenetics and related areas of molecular biology have eroded the exceptional status of the gene and presented the genome as fully interactive with the rest of the cell. Developmental systems theory provides a space for a vision of evolution that takes full account of the fundamental importance of developmental processes. Dupré shows the importance of microbiology for a proper (...) understanding of the living world, and reveals how it subverts such basic biological assumptions as the organisation of biological kinds on a branching tree of life, and the simple traditional conception of the biological organism. (shrink)

Two problems related to the biological identity of living beings are faced: the who-problem (which are the biological properties making that living being unique and different from the others?); the persistence-problem (what does it take for a living being to persist from a time to another?). They are discussed inside a molecular biology framework, which shows how epigenetics can be a good ground to provide plausible answers. That is, we propose an empirical solution to the who-problem and to the persistence-problem (...) on the basis of the new perspectives opened by a molecular understanding of epigenetic processes. In particular, concerning the former, we argue that any living being is the result of the epigenetic processes that have regulated the expression of its genome; concerning the latter, we defend the idea that the criterion for the persistence of its identity is to be indicated in the continuity of those epigenetic processes. We also counteract possible objections, in particular (1) whether our approach has something to say at a metaphysical level; (2) how it could account for the passage from the two phenotypes of the parental gametes to the single phenotype of the zygote; (3) how it could account for the identity of derivatives of one living being that continue to live disjoined from that original living being; (4) how it could account for higher mental functions. (shrink)

Graphical AbstractThe third annual meeting of the EpiGeneSys network brought together epigenetics and systems biologists to report on collaborative projects that apply quantitative approaches to understanding complex epigenetic processes. The figure shown represents one meeting highlight, which was the unexpected emergence of genotype versus epigenotype in control of cell state.

Nowadays in paleoanthropology it becomes more and more evident that the process of encephalopathy has guided our evolutionary line and that it can be investigated following two main strands of interpretation: the one based on selective mechanisms, which act on large numbers and in a completely random way, and the strand that constitutes the cornerstone of the Darwinian perspective on the evolution of life; or the one that is articulated according to a philosophical approach, aimed at formulating a "law of (...) complexity-consciousness," which, following Teilhard de Chardin's hypothesis, highlights the possible action, within the evolutionary mechanisms, of loadbearing lines of development, responsible for the "formation... (shrink)

Acute starvation can have long-term consequences that are mediated through epigenetic change. Some of these changes are affected by the activity of AMP-activated protein kinase, a master regulator of cellular energy homeostasis. In Caenorhabditis elegans, the absence of AMPK during a period of starvation in an early larval stage results in developmental defects following their recovery on food, while many of them become sterile. Moreover, the loss of AMPK during this quiescent period results in transgenerational phenotypes that can become (...) progressively worse with each successive generation. Our recent data describe a chromatin-based mechanism of how AMPK mediates adjustment to acute starvation in the germ cells, however, the heritable aspect of this AMPK mutant phenotype remains unresolved. Here, we explore how AMPK might affect this process and speculate how the initial transcription that occurs in the germ cells may adversely affect subsequent germline gene expression and/or genomic integrity. AMPK protects germ cell integrity during acute starvation by blocking inappropriate transcription. How these aberrant transcripts cause transgenerational defects is unclear. AMPK likely regulates germline integrity at multiple levels through several targets. The authors speculate here how AMPK disruption during starvation could result in the observed defects seen at each generation. (shrink)

In gestational surrogacy arrangements, the womb is often figured as a holding environment that brings the child of commissioning parents to fruition but does not shape fetal identity. This article probes the racial imaginary of such a figuration—what I term the “nonracializing womb”—where gestation is seen as peripheral to racial transmission. Drawing on feminist science studies frameworks and data from interviews with parents who commissioned surrogates, this article traces the cultural politics of the nonracializing womb, positioning it as an index (...) for broader understandings of race, reproductive labor, and kinship that hinge on nuclear and biogenetic forms. It then problematizes this figure of gestation by engaging emerging research on environmental epigenetics, which offers a lively model of pregnancy as shaping fetal biology, blurring the lines between surrogate and fetus. I argue that epigenetics offers a resource to reimagine gestation as a racializing process, by theorizing race not as solely genetic, but as relational, socio-environmental, and forged through distributed kinship lineages. (shrink)

ArgumentThe question, how organisms obtain their specific complex and functional forms, was widely discussed during the eighteenth century. The theory of preformation, which was the dominant theory of generation, was challenged by different alternative epigenetic theories. By the end of the century it was the vitalist approach most famously advocated by Johann Friedrich Blumenbach that prevailed. Yet the alternative theory of generation brought forward by Caspar Friedrich Wolff was an important contribution to the treatment of this question. He turned (...) his attention from the properties of matter and the forces acting on it towards the level of the processes of generation in order to explain the constitution of organismic forms. By regarding organic structures and forms to be the result of the lawfulness of ongoing processes, he opened up the possibility of a functional but non-teleological explanation of generation, and thereby provided an important complement to materialist and vitalist approaches. (shrink)

The notion that genetics, through natural selection, determines innate traits has led to much debate and divergence of thought on the impact of innate traits on the human phenotype. The purpose of this synthesis was to examine how innate theory informs genetic research and how understanding innate theory through the lens of Martha Rogers’ theory of unitary human beings can offer a contemporary view of how innate traits can inform epigenetic and genetic research. We also propose a new conceptual (...) model for genetic and epigenetic research. The philosophical, theoretical, and research literatures were examined for this synthesis. We have merged philosophical and conceptual phenomena from innate theory with the theory of unitary beings into the University of Illinois at Chicago model for genetic and epigenetic research. Innate traits are the cornerstone of the framework but may be modified epigenetically by biological, physiological, psychological, and social determinants as they are transcribed. These modifiers serve as important links between the concept of innate traits and epigenetic modifications, and, like the theory of unitary human beings, the process is understood in the context of individual and environmental interaction that has the potential to evolve as the determinants change. (shrink)

X‐chromosome inactivation ensures dosage compensation between the sexes in mammals by randomly choosing one out of the two X chromosomes in females for inactivation. This process imposes a plethora of questions: How do cells count their X chromosome number and ensure that exactly one stays active? How do they randomly choose one of two identical X chromosomes for inactivation? And how do they stably maintain this state of monoallelic expression? Here, different regulatory concepts and their plausibility are evaluated in the (...) context of theoretical studies that have investigated threshold behavior, ultrasensitivity, and bistability through mathematical modeling. It is discussed how a twofold difference between a single and a double dose of X‐linked genes might be converted to an all‐or‐nothing response and how mutually exclusive expression can be initiated and maintained. Finally, candidate factors that might mediate the proposed regulatory principles are reviewed. (shrink)

Here, the emerging data on DNA G‐quadruplexes (G4s) as epigenetic modulators are reviewed and integrated. This concept has appeared and evolved substantially in recent years. First, persistent G4s (e.g., those stabilized by exogenous ligands) were linked to the loss of the histone code. More recently, transient G4s (i.e., those formed upon replication or transcription and unfolded rapidly by helicases) were implicated in CpG island methylation maintenance and de novo CpG methylation control. The most recent data indicate that there are (...) direct interactions between G4s and chromatin remodeling factors. Finally, multiple findings support the indirect participation of G4s in chromatin reshaping via interactions with remodeling‐related transcription factors (TFs) or damage responders. Here, the links between the above processes are analyzed; also, how further elucidation of these processes may stimulate the progress of epigenetic therapy is discussed, and the remaining open questions are highlighted. (shrink)

The notion of antifragility, an attribute of systems that makes them thrive under variable conditions, has recently been proposed by Nassim Taleb in a business context. This idea requires the ability of such systems to ‘tinker’, i.e., to creatively respond to changes in their environment. A fairly obvious example of this is natural selection-driven evolution. In this ubiquitous process, an original entity, challenged by an ever-changing environment, creates variants that evolve into novel entities. Analyzing functions that are essential during stationary-state (...) life yield examples of entities that may be antifragile. One such example is proteins with flexible regions that can undergo functional alteration of their side residues or backbone and thus implement the tinkering that leads to antifragility. This in-built property of the cell chassis must be taken into account when considering construction of cell factories driven by engineering principles. (shrink)

Although the promyelocytic leukemia (PML) protein is renowned for regulating a wide range of cellular processes and as an essential component of PML nuclear bodies (PML‐NBs), the mechanisms through which it exerts its broad physiological impact are far from fully elucidated. Here, we review recent studies supporting an emerging view that PML's pleiotropic effects derive, at least partially, from its role in regulating histone H3.3 chromatin assembly, a critical epigenetic mechanism. These studies suggest that PML maintains heterochromatin organization (...) by restraining H3.3 incorporation. Examination of PML's contribution to H3.3 chromatin assembly in the context of the cell cycle and PML‐NB assembly suggests that PML represses heterochromatic H3.3 deposition during S phase and that transcription and SUMOylation regulate PML's recruitment to heterochromatin. Elucidating PML’ s contributions to H3.3‐mediated epigenetic regulation will provide insight into PML's expansive influence on cellular physiology and open new avenues for studying oncogenesis linked to PML malfunction. (shrink)

This paper builds upon historico-epistemological analyses of plasticity across the nineteenth and twentieth centuries to distinguish among uses of this notion in contemporary epigenetics. By digging into this diachronic phase of plasticity thinking, we highlight a series of historically situated understandings and pragmatic dimensions of this notion. Specifically, our analysis describes four distinct phases in plasticity thinking across the nineteenth and twentieth centuries: plasticity as chemical modification of the body by its milieu; plasticity as explanandum for the modifications of life’s (...) ontogenetic and phylogenetic substrates; plasticity as mechanistic process in need of distinct explanations in ontogeny and phylogeny; and plasticity as responsive potential to perturbations of a complex genetic system of development. These four versions of plasticity provide, in turn, the opportunity to discern synchronically the uses of this notion in epigenetic biosciences. Fleshing out these historical ramifications animating the present, we argue, highlights a fundamental epistemological disagreement at the basis of the controversies around the definition, scope, and epistemic priorities of epigenetics: how to reconcile the contemporary epistemologies of plasticity that hold epigenetic marks capable of bearing the material impression of the environment with those grounded on a strong view of plasticity as operating under genetic control? Parallel to this analysis of the epistemic space of plasticity from the nineteenth century onward, we show how these distinct modes of understanding body–environment relationships also constituted conceptual, representational, and experimental resources for understanding the entanglement between life as a biological and socially situated phenomenon. These different traces of biosocial thinking ante litteram, we conclude, provide a blueprint to interrogate today’s assumptions, values, ontologies, and political leanings behind similar attempts to interpret the biosocial nexus that links our biology with its material, social, and cultural environments. (shrink)

Whiteheadian concepts of life, food, "empty" and "occupied space" provide a theoretical basis to unpack an ontogenetic perspective on aging. Focusing on the so-called "Selective Optimization with Compensation " strategy, this work will explore this concept in relation to some scientific evidence in the fields of "epigenetics " and molecular nutrition. Further, the role of caloric restriction in health and longevity will be discussed as a SOC strategy, based on the metabolic theory of aging. SOC strategy applied to the (...) class='Hi'>processes of aging, when linked with Whitehead's philosophy of organism, makes it possible for us to think about life as a selective process provided by "empty space. " A continuum within the physical field optimizes a "living society," which evolves in permanent social deficit, by means of compensation by nutritional metabolism. (shrink)

Griffiths and Stotz’s Genetics and Philosophy: An Introduction offers a very good overview of scientific and philosophical issues raised by present-day genetics. Examining, in particular, the questions of how a “gene” should be defined and what a gene does from a causal point of view, the authors explore the different domains of the life sciences in which genetics has come to play a decisive role, from Mendelian genetics to molecular genetics, behavioural genetics, and evolution. In this review, I highlight what (...) I consider as the two main theses of the book, namely: genes are better conceived as tools; genes become causes only in a context. I situate these two theses in the wider perspective of developmental systems theory. This leads me to emphasize that Griffiths and Stotz reflect very well an on going process in genetics, which I call the “epigenetization” of genetics, i.e., the growing interest in the complex processes by which gene activation is regulated. I then make a factual objection, which is that Griffiths and Stotz have almost entirely neglected the perspective of ecological developmental biology, and more precisely recent work on developmental symbioses, and I suggest that this omission is unfortunate in so far as an examination of developmental symbioses would have considerably strengthened Griffiths and Stotz’s own conclusions. (shrink)

Notch signaling plays an essential role in the processes of embryogenesis and cellular differentiation, and it is believed that the oncogenic effects of dysregulated Notch signaling are an anomalous reflection of the normal functions of this cascade. Nonetheless, the cellular events associated with oncogenic Notch signaling have thus far remained elusive. In a recent report, Ferres‐Marco et al.1 described how they used the Drosphila eye as a model system and found that elevated Notch signaling in combination with activation of (...) components of the Polycomb complex of transcriptional repressors led to metastatic growth of tumors through epigenetic silencing of the Rbf gene. Rbf is the Drosophila homologue of the retinoblastoma tumor‐suppressor gene (Rb), thus it represents a novel link between Notch signaling, tumor growth and metastasis. BioEssays 28: 692–695, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

We here review primary methods used in quantifying and mapping 5‐hydroxymethylcytosine (5hmC), including global quantification, restriction enzyme‐based detection, and methods involving DNA‐enrichment strategies and the genome‐wide sequencing of 5hmC. As discovered in the mammalian genome in 2009, 5hmC, oxidized from 5‐methylcytosine (5mC) by ten‐eleven translocation (TET) dioxygenases, is increasingly being recognized as a biomarker in biological processes from development to pathogenesis, as its various detection methods have shown. We focus in particular on an ultrasensitive single‐molecule imaging technique that can (...) detect and quantify 5hmC from trace samples and thus offer information regarding the distance‐based relationship between 5hmC and 5mC when used in combination with fluorescence resonance energy transfer. (shrink)

The nature of “the self” has been one of the central problems in philosophy and more recently in neuroscience. This raises various questions: Can we attribute a self to animals? Do animals and humans share certain aspects of their core selves, yielding a trans-species concept of self? What are the neural processes that underlie a possible trans-species concept of self? What are the developmental aspects and do they result in various levels of self-representation? Drawing on recent literature from both (...) human and animal research, we suggest a trans-species concept of self that is based upon what has been called a “core-self” which can be described by self-related processing as a specific mode of interaction between organism and environment. When we refer to specific neural networks, we will here refer to the underlying system as the “core-SELF.” The core-SELF provides primordial neural coordinates that represent organisms as living creatures—at the lowest level this elaborates interoceptive states along with raw emotional feelings while higher medial cortical levels facilitate affective-cognitive integration . Developmentally, SRP allows stimuli from the environment to be related and linked to organismic needs, signaled and processed within core-self structures within subcorical-cortical midline structures that provide the foundation for epigenetic emergence of ecologically framed, higher idiographic forms of selfhood across different individuals within a species. These functions ultimately operate as a coordinated network. We postulate that core SRP operates automatically, is deeply affective, and is developmentally and epigenetically connected to sensory-motor and higher cognitive abilities. This core-self is mediated by SCMS, embedded in visceral and instinctual representations of the body that are well integrated with basic attentional, emotional and motivational functions that are apparently shared between humans, non-human mammals, and perhaps in a proto-SELF form, other vertebrates. Such a trans-species concept of organismic coherence is thoroughly biological and affective at the lowest levels of a complex neural network, and culturally and ecologically molded at higher levels of neural processing. It allows organisms to selectively adapt to and integrate with physical and social environments. Such a psychobiologically universal, but environmentally diversified, concept may promote novel trans-species studies of the core-self across mammalian species. (shrink)

Phylogenetic, epigenetic, and neurophysiological data characterize the specificity and limitations of the systems that support individual face recognition in human and non-human primates. The central question of the recognition of the faces of other species explores the processes that lead to the remarkable face expertise that humans and non-humans develop for members of their own species. This article reviews the literature on categorization/recognition abilities within and across species in human and non-human primates. It evaluates whether it is possible (...) for a species to perceive other species faces at the same level of expertise as for their own species. The neural substrate and the current models of neuronal processing that support face processing in human and non-human primates are described. Finally, it discusses the developmental data pertaining to face processing in human and non-human primates, challenging the view that face processing can be plastic in adults. (shrink)

This article develops a media philosophical framework for addressing the intersection of epigenetics and complex dynamical systems in theoretical biology. In particular, it argues that the theoretical humanities need to think critically about the computability of epigenomic regulation, as well as speculatively about the possibility of an epigenomics beyond complexity. The fact that such a conceptual framework does not exist suggests not only a failure to engage with the mathematics of complexity, but also a failure to engage with its history. (...) Both epigenetics and the application of complex dynamical systems to biology originate in the mid-twentieth-century work of Conrad Hal Waddington. The article demonstrates how this genealogy of epigenetic complexity reveals the need for a speculative conception of epigenomic mediation beyond mathematical complexity. Using Whitehead’s philosophy as a conceptual anchor, the “epimedial landscape” serves as a first pass at a media philosophical revision of the complex dynamical systems view of the epigenetic landscape. (shrink)

The current mainstream in cancer research favours the idea that malignant tumour initiation is the result of a genetic mutation. Tumour development and progression is then explained as a sort of micro-evolutionary process, whereby an initial genetic alteration leads to abnormal proliferation of a single cell that leads to a population of clonally derived cells. It is widely claimed that tumour progression is driven by natural selection, based on the assumption that the initial tumour cells acquire some properties that endow (...) such cells with a selective advantage over the normal cells from which the tumour cells are derived. The standard view assumes that the transformed bodily cell somehow acquires "responsiveness" to natural selection independently of the whole organism to which the cell belongs. Yet, it is never explained where such an acquired capacity to respond to natural selection by the individual bodily cell comes from. This situation poses many difficult questions that so far have been left unanswered. For example, there is no explanation why some cells belonging to an organised whole and as such having no independent capacity for survival, apparently become 'independent' entities, able to respond to selective pressures in an autonomous fashion and then to be evaluated by natural selection. Hereunder it is argued that such a qualitative change cannot be the consequence of specific genetic mutations. Moreover, it is shown that natural selection is unlikely to be acting within the organism during tumour development and progression and that tumour evolution is a random, non-adaptive process, driven by no fundamental biological principle. Thus, mutations in the so-called oncogenes and tumour suppressor genes observed in epithelial cancers (that constitute more than 90% of all cancers) are not the result of selection for better cellular growth or survival under restrictive conditions. Instead, here it is suggested that they are the consequence of genetic drift acting upon gene functions that become non-relevant, either for the individual or the species fitness, once the organism is past its reproductive prime and as such, they also become superfluous for cell survival in the short term. It is proposed that the origin of cancer is epigenetic and it is a consequence of the need for a continued turnover of the individuals that constitute a species. (shrink)

Many models of evolution are implicitly causal processes. Features such as causal feedback between evolutionary variables and evolutionary processes acting at multiple levels, though, mean that conventional causal models miss important phenomena. We develop here a general theoretical framework for analyzing evolutionary processes drawing on recent approaches to causal modeling developed in the machine-learning literature, which have extended Pearls do-calculus to incorporate cyclic causal interactions and multilevel causation. We also develop information-theoretic notions necessary to analyze causal information (...) dynamics in our framework, introducing a causal generalization of the Partial Information Decomposition framework. We show how our causal framework helps to clarify conceptual issues in the contexts of complex trait analysis and cancer genetics, including assigning variation in an observed trait to genetic, epigenetic and environmental sources in the presence of epigenetic and environmental feedback processes, and variation in fitness to mutation processes in cancer using a multilevel causal model respectively, as well as relating causally-induced to observed variation in these variables via information theoretic bounds. In the process, we introduce a general class of multilevel causal evolutionary processes which connect evolutionary processes at multiple levels via coarse-graining relationships. Further, we show how a range of fitness models can be formulated in our framework, as well as a causal analog of Prices equation, clarifying the relationships between realized/probabilistic fitness and direct/indirect selection. Finally, we consider the potential relevance of our framework to foundational issues in biology and evolution, including supervenience, multilevel selection and individuality. Particularly, we argue that our class of multilevel causal evolutionary processes, in conjunction with a minimum description length principle, provides a conceptual framework in which identification of multiple levels of selection may be reduced to a model selection problem. (shrink)

The evolution of the human brain has resulted in the emergence of higher-order cognitive abilities, such as reasoning, planning and social awareness. Although there has been a concomitant increase in brain size and complexity, and component diversification, we argue that RNA regulation of epigenetic processes, RNA editing, and the controlled mobilization of transposable elements have provided the major substrates for cognitive advance. We also suggest that these expanded capacities and flexibilities have led to the collateral emergence of psychiatric (...) fragilities and conditions. (shrink)

In this paper it is analyzed from the informational perspective the relation between mind and body, an ancient philosophic issue defined as a problem, which still did not receive up to date an adequate solution. By introducing/using the concept of information, it is shown that this concept includes two facets, one of them referring to the common communications and another one referring to a hidden/structuring matter-related information, effectively acting in the human body and in the living systems, which determines the (...) dynamic inter-change of information between specific structures of the organism by electric/electronic/chemical agents and genetic/epigenetic processes. It is shown that the maintenance of body, permanently and obligatory depending on the external matter (foods, air, water) resources, needed to provide both the structuring/restructuring basic material and energy, determines the necessary existence of an info-managing system, administrating the internal mechano-chemical/physical processes. As a natural consequence, such a system should organize and assure own survival by an effective informational operability to detect the external food resources, to select the appropriate interest information and to decide as a function of circumstances. One important component in such an informational system is memory, allowing to dispose of the reference informational data for analysis/comparison and the selection between good and bad binary possible decisions. The memory receives and stores therefore signals from external reality and from the body itself, referring to the emotional reaction, digestion status, creation, and inherited predilections, within specific info-neural communication circuits between the brain and body execution/sensitive organs, the human body appearing as an integrated info-matter self-managed dynamic system. The specific body components memorize information with different degrees of info-integration: short/long-term integration, emotive/action reaction, info-abilities, culminating with the integration in the chromosomal structures by epigenetic processes. The new acquired information is transgenerationally transmissible, and is manifested as new traits, showing the adaptation capability of the human and close relation between mind and body. Analyzing the results of such a mind-body informational model in comparison with the earlier assumed/proposed/asserted archaic, Greek and Occidental philosophies, which represent only partial aspects of this relation, it is shown that this informational model, elaborated in terms of information on the basis of scientific reasons and arguments, constitutes a general, realist, and coherent model of the mind-body relation, able to integrate and/or explain most of the others. (shrink)

Embryonic development and ontogeny occupy whatis often depicted as the black box betweengenes – the genotype – and the features(structures, functions, behaviors) of organisms– the phenotype; the phenotype is not merelya one-to-one readout of the genotype. Thegenes home, context, and locus of operation isthe cell. Initially, in ontogeny, that cell isthe single-celled zygote. As developmentensues, multicellular assemblages of like cells(modules) progressively organized as germlayers, embryonic fields, anlage,condensations, or blastemata, enable genes toplay their roles in development and evolution.As modules, condensations are (...) fundamentaldevelopmental and selectable units ofmorphology (morphogenetic units) that mediateinteractions between genotype and phenotype viaevolutionary developmental mechanisms. In ahierarchy of emergent processes, gene networksand gene cascades (genetic modules) link thegenotype with morphogenetic units such ascondensations, while epigenetic processes suchas embryonic inductions, tissue interactionsand functional integration, link morphogeneticunits to the phenotype. To support theseconclusions I distinguish units of heredityfrom units of transmission and discussepigenetic inheritance by tracing the historyof relationship between embryology andevolution, especially the role(s) assigned tocells or to cellular components in generatingtheories of morphological change in evolution.The concept of cells as modular morphogeneticunits is modeled and illustrated using themammalian dentary bone. (shrink)

The linear sequence specification of a gene product is not provided by the target DNA sequence alone but by the mechanisms of gene expressions. The main actors of these mechanisms, proteins and functional RNAs, relay environmental information to the genome with important consequences to sequence selection and processing. This `postgenomic' reality has implications for our understandings of development not as predetermined by genes but as an epigenetic process. Critics of genetic determinism have long argued that the activity of `genes' (...) and hence their contribution to the phenotype depends on intra- and extraorganismal `environmental' elements. As will be shown here, even the mere physical existence of a `gene' is dependent on its phenotypic context. (shrink)