Transcriptional silencing may not necessarily depend on the continuous residence of a sequence‐specific repressor at a control element and may act via a “hit and run” mechanism. Due to limitations in assays that detect transcription factor (TF) binding, such as chromatin immunoprecipitation followed by high‐throughput sequencing (ChIP‐seq), this phenomenon may be challenging to detect and therefore its prevalence may be underappreciated. To explore this possibility, erythroid gene promoters that are regulated directly by GATA1 in an inducible system are analyzed. It (...) is found that many regulated genes are bound immediately after induction of GATA1 but the residency of GATA1 decreases over time, particularly at repressed genes. Furthermore, it is shown that the repressive mark H3K27me3 is seldom associated with bound repressors, whereas, in contrast, the active (H3K4me3) histone mark is overwhelmingly associated with TF binding. It is hypothesized that during cellular differentiation and development, certain genes are silenced by repressive TFs that subsequently vacate the region. Catching such repressor TFs in the act of silencing via assays such as ChIP‐seq is thus a temporally challenging prospect. The use of inducible systems, epitope tags, and alternative techniques may provide opportunities for detecting elusive “hit and run” transcriptional silencing. Also see the video abstract here https://youtu.be/vgrsoP_HF3g. (shrink)

People with a repressive coping style are highly motivated to defend themselves against self-concept threats. But what kinds of unfavourable personal characteristics are they most focused on avoiding? Weinberger (Citation1990) suggested that repressors are primarily concerned with seeing themselves (and having others see them) as calm, unemotional people who are not prone to experiencing negative affect. A content analysis of the actual (self-ascribed) and undesired attributes of 349 male and female college students, however, provided no support for that hypothesis. (...) Instead, relative to other participants, repressors’ undesired selves consisted more of traits exemplifying disagreeableness (as defined by the five-factor model). Repressors might not engage in affective self-regulation for its own sake, but because it allows them to control expression of traits with which they are more directly concerned. (shrink)

A fascinating property of germ cells is their ability to maintain totipotency throughout development. At fertilization, this totipotency is unleashed and the egg generates all the cell types needed to make a brand new organism. Occasionally, germ cells differentiate precociously in the embryo or in the gonads and form teratomas, tumors containing many differentiated somatic cell types. Until recently, the genetic basis for teratoma formation was not known. The unexpected discovery of a teratoma in a C. elegans double mutant points (...) to translational control as a key mechanism to maintain totipotency in developing germ cells. BioEssays 28: 865–867, 2006. © 2006 Wiley periodicals, Inc. (shrink)

Certain sequences of double‐helical DNA can be recognized and tightly bound by oligonucleotides. The effects of such triple‐helical structures on DNA binding proteins have been studied. Stabilities of DNA triple‐helices at or near physiological conditions are sufficient to inhibit DNA binding proteins directed to overlapping sites. Such proteins include restriction endonucleases, methylases, transcription factors, and RNA polymerases. These and Other results suggest that oligonucleotide‐directed triple‐helix formation could provide the basis for designing artificial gene repressors. The general question of whether (...) biological systems employ RNA molecules for recognition and regulation of double‐helical DNA is discussed. (shrink)

Two putative functions of emotion experience — its roles in intentional action and in social understanding — were investigated using a group of individuals (repressors) known to have impaired anxiety experience. Repressors, low-anxious, high-anxious, and defensive high-anxious individuals were asked to give a public presentation, and then given the opportunity to avoid the presentation. Repressors were the group most likely to avoid giving the presentation, but were the least likely to give an emotional explanation for their avoidance. (...) By contrast, they were not less likely than other groups to provide negative emotional explanations of another person’s behaviour in a film clip. We concluded that: (1) repressors are impaired in self- but not in other-explanation using emotion, implying that “simulation” is not the method used by repressors to ground their folk psychology, (2) the intentional avoidance shown by repressors is indicative of some intact first-order phenomenal anxiety experience but that they lack second-order awareness of this anxiety experience. (shrink)

Innovative loss‐of‐function techniques developed in recent years have made it much easier to target specific genomic loci at transcriptional levels. CRISPR interference (CRISPRi) has been proven to be the most effective and specific tool to knock down any gene of interest in mammalian cells. The catalytically deactivated Cas9 (dCas9) can be fused with transcription repressors to downregulate gene expression specified by sgRNA complementary to target genomic sequence. Although CRISPRi has huge potential for gene knockdown, there is still a lack (...) of systematic guidelines for efficient and widespread use. Here we describe the working mechanism and development of CRISPRi, designing principles of sgRNA, delivery methods and applications in mammalian cells in detail. Finally, we propose possible solutions and future directions with regard to current challenges. (shrink)

In the above pages I have sketched a history of the genesis and comparative evaluation of the repressor model of genetic regulation of enzyme induction. I have not attempted in this article to carry out an analysis of the more scientifically interesting fully developed Jacob-Monod operon theory of genetic regulations but such an analysis of the operon theory would not, I believe, involve any additional logical or epistemological features than have been discussed above. I have argued that the above account (...) of the development of a theory of enzyme induction involved inferential moves and well-characterized desiderata, of both empirical and non-empirical character, in the genesis and evaluation of new hypotheses and theories. I have also contended that the reasoning displayed in the genesis of a theory is in a large measure identical to that utilized in evaluating a theory. Both of these conclusions are at variance with the views of philosophers such as H. Reichenbach, Sir Karl Popper, and C.G. Hempel who have argued that the genesis of new hypotheses is primarily an irrational affair and that only the context of justification is susceptible of rational reconstruction. In the alternative view presented here, scientific discovery and scientific justification represent the application in contexts, which are primarily telically distinguishable, of a fundamentally unitary logic of scientific inquiry. (shrink)

Participants scoring high and low on a measure of repressive coping style (Mendolia, 2002) first learned a series of related word pairs (cue–target). Half of the cues were homographs. In the subsequent think/no-think phase (Anderson & Green, 2001), they responded with targets on some trials and suppressed thoughts of targets on others. Suppressed targets were always emotionally negative, as were targets associated with baseline cues reserved for the final test. Some participants were provided with emotionally benign or positive substitutes to (...) help them suppress, and these substitutes were related to different meanings of the homographic cues, compared to those established by the targets. On the final test, all cues were presented for target recall. Only the repressors significantly benefited from the provision of positive substitutes to aid forgetting of the negative targets, regardless of the nature of the cues. (shrink)

Homeotic genes are subject to transcriptional silencing, which prevents their expression in inappropriate body regions. Here, we shall focus on Drosophila, as little is known about this process in other organisms. Evidence is accumulating that silencing of Drosophila homeotic genes is conferred by two types of cis‐regulatory sequences: initiation (SIL‐I) and maintenance (SIL‐M) elements. The former contain target sites for transient repressors with a highly localised distribution in the early embryo and the latter for constitutive repressors that are (...) likely to be present in all cells. We discuss how SIL‐I elements may cooperate with SIL‐M elements to promote formation of a silencing complex. We propose that this complex consists of specific non‐histone proteins, the so‐called Polycomb group proteins, and that it is anchored at SIL‐M elements and at the promoter. (shrink)

Transcription factor (TF) signaling regulates gene transcription and requires a complex network of proteins. This network includes co‐activators, co‐repressors, multiple TFs, histone‐modifying complexes, and the basal transcription machinery. It has been widely appreciated that pioneer factors, such as FoxA1 and GATA1, play an important role in opening closed chromatin regions, thereby allowing binding of a secondary factor. In this review we will focus on a newly proposed model wherein multiple TFs, such as steroid receptors (SRs), can function in a (...) pioneering role. This model, termed dynamic assisted loading, integrates data from widely divergent methodologies, including genome wide ChIP‐Seq, digital genomic footprinting, DHS‐Seq, live cell protein dynamics, and biochemical studies of ATP‐dependent remodeling complexes, to present a real time view of TF chromatin interactions. Under this view, many TFs can act as initiating factors for chromatin landscape programming. Furthermore, enhancer and promoter states are more accurately described as energy‐dependent, non‐equilibrium steady states. (shrink)

Two putative functions of emotion experience ? its roles in intentional action and in social understanding ? were investigated using a group of individuals (repressors) known to have impaired anxiety experience. Repressors, low-anxious, high-anxious, and defensive high-anxious individuals were asked to give a public presentation, and then given the opportunity to avoid the presentation. Repressors were the group most likely to avoid giving the presentation, but were the least likely to give an emotional explanation for their avoidance. (...) By contrast, they were not less likely than other groups to provide negative emotional explanations of another person?s behaviour in a film clip. We concluded that: (1) repressors are impaired in self- but not in other-explanation using emotion, implying that ?simulation? is not the method used by repressors to ground their folk psychology, (2) the intentional avoidance shown by repressors is indicative of some intact first-order phenomenal anxiety experience but that they lack second-order awareness of this anxiety experience. (shrink)

Much of the current imaging literature either denies the existence of wakeful non-mental imagers, views non-imagers motivationally as 'repressors' or 'neurotic', or acknowledges them but does not fully incorporate them into their models. Neurobiologists testing for imaging loss seem to assume that visual recognition, describing objects, and free-hand drawing require the forming of conscious images. The intuition that 'the psyche never thinks without an image.... the reasoning mind thinks its ideas in the form of images' (Aristotle) has a long (...) tradition in philosophical psychology, from Aristotle through the British empiricists to the British-empiricist-inspired introspection paradigm of Titchener. The massive shift in early experimental psychology to the introspective-antagonistic paradigm of Watson's behaviourism, may have sprung from the contrary intuition that no one thinks in mental images. In both cases, people seemed to assume that what is in one's own mind is in everybody's mind. A third, mediating, intuition - that some people do not think with conscious mental imagery -- seems to be confirmed by empirical studies on many levels. From the early imagery interviews of Francis Galton through many modern surveys, including my own, a consistent diversity of self-reports on ones own mental imagery abilities suggests that some 2-5% of people are very poor- or non-visual- imagers who, yet, maintain normal visual recognition abilities. Comparable estimates have been made in auditory and other imagery modalities. (shrink)

The transcription factor Nrf2 is the master regulator of cellular stress response, facilitating the expression of cytoprotective genes, including those responsible for drug detoxification, immunomodulation, and iron metabolism. FDA‐approved Nrf2 activators, Tecfidera and Skyclarys for patients with multiple sclerosis and Friedreich's ataxia, respectively, are non‐specific alkylating agents exerting side effects. Nrf2 is under feedback regulation through its target gene, transcriptional repressor Bach1. Specifically, in Parkinson's disease and other neurodegenerative diseases with Bach1 dysregulation, excessive Bach1 accumulation interferes with Nrf2 activation. Bach1 (...) is a heme sensor protein, which, upon heme binding, is targeted for proteasomal degradation, relieving the repression of Nrf2 target genes. Ideally, a combination of Nrf2 stabilization and Bach1 inhibition is necessary to achieve the full therapeutic benefits of Nrf2 activation. Here, we discuss recent advances and future perspectives in developing small molecule inhibitors of Bach1, highlighting the significance of the Bach1/Nrf2 signaling pathway as a promising neurotherapeutic strategy. (shrink)

Many targets of the Wnt/β-catenin signaling pathway are regulated by TCF transcription factors, which play important roles in animal development, stem cell biology, and oncogenesis. TCFs can regulate Wnt targets through a “transcriptional switch,” repressing gene expression in unstimulated cells and promoting transcription upon Wnt signaling. However, it is not clear whether this switch mechanism is a general feature of Wnt gene regulation or limited to a subset of Wnt targets. Co-repressors of the TLE family are known to contribute (...) to the repression of Wnt targets in the absence of signaling, but how they are inactivated or displaced by Wnt signaling is poorly understood. In this mini-review, we discuss several recent reports that address the prevalence and molecular mechanisms of the Wnt transcription switch, including the finding of Wnt-dependent ubiquitination/inactivation of TLEs. Together, these findings highlight the growing complexity of the regulation of gene expression by the Wnt pathway. Wnt targets are regulated by a “switch” where TLE co-repressors are displaced from TCFs by β-catenin, leading to activation of transcription. Recent reports challenge this view and suggest that additional processes, including exchange of specific TCF proteins and Wnt-dependent ubiquitination of TLEs, play important roles in the Wnt transcriptional switch. (shrink)

Pleiotropically acting eukaryotic corepressors such as retinoblastoma and SIN3 have been found to physically interact with many widely expressed “housekeeping” genes. Evidence suggests that their roles at these loci are not to provide binary on/off switches, as is observed at many highly cell‐type specific genes, but rather to serve as governors, directly modulating expression within certain bounds, while not shutting down gene expression. This sort of regulation is challenging to study, as the differential expression levels can be small. We hypothesize (...) that depending on context, corepressors mediate “soft repression,” attenuating expression in a less dramatic but physiologically appropriate manner. Emerging data indicate that such regulation is a pervasive characteristic of most eukaryotic systems, and may reflect the mechanistic differences between repressor action at promoter and enhancer locations. Soft repression may represent an essential component of the cybernetic systems underlying metabolic adaptations, enabling modest but critical adjustments on a continual basis. (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)

Fezf1 and Fezf2 are highly conserved transcription factors that were first identified by their specific expression in the anterior neuroepithelium of Xenopus and zebrafish embryos. These proteins share an N‐terminal domain with homology to the canonical engrailed repressor motif and a C‐terminal DNA binding domain containing six C2H2 zinc‐finger repeats. Over a decade of study indicates that the Fez proteins play critical roles during nervous system development in species as diverse as fruit flies and mice. Herein we discuss recent progress (...) in understanding the functions of Fezf1 and Fezf2 in neurogenesis and cell fate specification during mammalian nervous system development. Going forward we believe that efforts should focus on understanding how expression of these factors is precisely regulated, and on identifying target DNA sequences and interacting partners. Such knowledge may reveal the mechanisms by which Fezf1 and Fezf2 accomplish both independent and redundant functions across diverse tissue and cell types. (shrink)

A myriad of coordinated signals control cellular differentiation. Reprogramming the cell's proteome drives global changes in cell morphology and function that define cell phenotype. A switch in alternative splicing of many pre‐mRNAs encoding neuronal‐specific proteins accompanies neuronal differentiation. Three groups recently showed that the global splicing repressor, polypyrimidine track‐binding protein (PTB), regulates this switch.1-3 Although a subset of neuronal genes are turned on in both non‐neuronal and neuronal cells, restricted expression of PTB in non‐neuronal cells diverts their mRNAs to nonsense‐mediated (...) decay and prevents protein expression. When the PTB brake is released, the cell splices like a neuron. BioEssays 30:1–4, 2008. © 2007 Wiley Periodicals, Inc. (shrink)

The Polycomb group of proteins (PcGs) are transcriptional repressor complexes that regulate important biological processes and play critical roles in cancer. Mutating or deleting EZH2 can have both oncogenic and tumor suppressive functions by increasing or decreasing H3K27me3. In contrast, mutations of SUZ12 and EED are reported to have tumor suppressive functions. EZH2 is overexpressed in many cancers, including prostate cancer, which can lead to silencing of tumor suppressors, genes regulating epithelial to mesenchymal transition (EMT), and interferon signaling. In some (...) cases, EZH2 overexpression also leads to its use of non‐histone substrates. Lastly, PRC2 associated factors can influence the progression of cancer through progressive mutations or by specific binding to certain target genes. Here, we discuss which mutations and deletions of the PRC2 complex have been detected in different cancers, with a specific focus on the overexpression of EZH2 in prostate cancer. (shrink)

The Pajama (Pardee, Jacob, Monod) experiment provided a breakthrough in our understanding of the molecular mechanisms by which gene expression is regulated. Today, twenty‐five years later it provides a paradigm for thinking about problems of gene expression, such as growth regulation and differentiation. From this experiment emerged entities such as repressors, regulatory genes, the operon as a group of jointly controlled genes, and messenger RNA.

Several molecular mechanisms contribute directly and mechanically to the loss of epithelial phenotype. During epithelial–mesenchymal transition (EMT), adherens junctions and desmosomes are at least partially dissociated. At the same time, a massive cytoskeleton reorganization takes place, involving the rho family and the remodeling of the actin microfilament mesh. Numerous pathways have been described in vitro that control phenotype transition in specific cell models. In vivo developmental studies suggest that transcriptional control, activated by a specific pathway involving Ras, Src and potentially (...) the Wnt pathway, is an essential step. Recent functional and localization experiments indicate that the slug/snail family of transcription factors functions overall as an epithelial phenotype repressor and could represent a key EMT contributor. BioEssays 23:912–923, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

The transcriptional co‐activators YAP (or YAP1) and TAZ (or WWTR1) are frequently activated during the growth and progression of many solid tumors, including lung, colorectal, breast, pancreatic, and liver carcinomas as well as melanoma and glioma. YAP/TAZ bind to TEAD‐family co‐activators to drive cancer cell survival, proliferation, invasive migration, and metastasis. YAP/TAZ activation may also confer resistance to chemotherapy, radiotherapy, or immunotherapy. YAP‐TEAD cooperates with the RAS‐induced AP‐1 (FOS/JUN) transcription factor to drive tumor growth and cooperates with MRTF‐SRF to promote (...) activation of cancer‐associated fibroblasts, matrix stiffening, and metastasis. The key upstream repressor of YAP/TAZ activation is the Hippo (MST1/2‐LATS1/2) pathway and the key upstream activators are mechanically induced Integrin‐SRC and E‐cadherin‐AJUBA/TRIP6/LIMD1, growth factor induced PI3K‐AKT, and inflammation‐induced G‐protein coupled receptor (GPCR) signals, all of which antagonize the Hippo pathway. In this review, strategies to target YAP/TAZ activity in cancer are discussed along with the prospects for synergy with established pillars of cancer therapy. (shrink)

Knockout experiments in Tetrahymena show that linker histone H1 is not essential for nuclear assembly or cell viability. These results, together with a series of biochemical and cell biological observations, challenge the existing paradigm that requires linker histones to be a key organizing component of higher‐order chromatin structure. The H1 Knockouts also reveal a much more subtle role for H1. Instead of acting as a general transcriptional repressor, H1 is found to regulate a limited number of specific genes. Surprisingly, H1 (...) can both activate and repress transcription. We discuss how this architectural protein might accomplish this important regulatory role. (shrink)

The expression of epithelial cell adhesion and cytoskeletal genes is orchestrated by an apparently unique set of rules. No tissue‐specific transactivator proteins have been found to drive them; only ubiquitous factors are utilized. In non‐epithelial cells, they are actively repressed. Moreover, it was recently found that a single protein (adenovirus E1a) coordinately represses non‐epithelial genes while inducing epithelial genes. A simple model is offered to explain how epithelial gene expression is coordinated. Under this model, the epithelial cell gene expression program (...) is a transcriptional ‘default’; that is, it occurs in the absence of tissue‐specific transactivation. Conversion to this default requires only that mesenchymal transactivators are not expressed, or that central ‘integrator’ proteins are inactive. In their absence, mesenchymal gene expression cannot occur. Moreover, because the repressors cease to be expressed, the epithelial genes are induced. Oncogenes generally cause the breakdown of the epithelial phenotype ‐ generating carcinomas ‐ so genes such as E1a that cause epithelial conversion may prove useful for both understanding and controlling cancer. (shrink)

Werner syndrome (WS) is an inherited disorder that produces somatic stunting, premature ageing and early onset of degenerative and neoplastic diseases. Cultured fibroblasts derived from subjects with WS are found to undergo premature replicative senescence and thus provide a cellular model system to study the disorder. Recently, several overexpressed gene sequences isolated from a WS fibroblast cDNA library have been shown to possess the capacity to inhibit DNA synthesis and disrupt many normal biochemical processes. Because a similar constellation of genes (...) is overexpressed in WS and senescent normal fibroblasts, these data suggest the existence of a common molecular genetic pathway for replicative senescence in both types of cell. We propose that the primary defect in WS is a mutation in a gene for a trans‐acting repressor protein that reduces its binding affinity for shared regulatory regions of several genes, including those that encode inhibitors of DNA synthesis (IDS). The mutant WS repressor triggers a sequence of premature expression of IDS and other genes, with resulting inhibition of DNA synthesis and early cellular senescence, events which occur much later in normal cells. (shrink)

CtBP family proteins predominantly function as transcriptional corepressors. Studies with mutant mouse suggest that the two mouse genes, Ctbp1 and Ctbp2, play unique and redundant gene regulatory roles during development.1 Ctbp1-deficient mice are viable, but are small and die early, while Ctbp2 deficiency leads to embryonic lethality. Ctbp2-null mutation causes defects in axial patterning, heart morphogenesis and neural development. The Ctbp2 mutant phenotype is more severe in the absence of Ctbp1. The studies with Ctbp2 mutant embryos suggest that CtBP can (...) also activate transcription. A plant CtBP homolog, Angustifolia (AN), has recently been identified.2, 3 AN controls polar elongation of leaf cells via the microtubule cytoskeleton. Microarray analysis suggests that AN also functions as a transcriptional repressor. Thus, the CtBP family proteins control cellular processes by serving as transcriptional activators and regulators of the cytoskeleton as well as transcriptional corepressors. BioEssays 25:9–12, 2003. © 2002 Wiley Periodicals, Inc. (shrink)

Hedgehog (HH) signaling is a conserved pathway that drives developmental growth and is essential for the formation of most organs. The expression of HH target genes is regulated by a dual switch mechanism where GLI proteins function as bifunctional transcriptional activators (in the presence of HH signaling) and transcriptional repressors (in the absence of HH signaling). This results in a tight control of GLI target gene expression during rapidly changing levels of pathway activity. It has long been presumed that (...) GLI proteins also repress target genes prior to the initial expression of HH in a given tissue. This idea forms the basis for the limb bud pre‐patterning model for regulating digit number. Recent findings indicate that GLI repressor proteins are indeed present prior to HH signaling but contrary to this model, GLI proteins are inert as they do not regulate transcriptional responses or enhancer chromatin modifications at this time. These findings suggest that GLI transcriptional repressor activity is not a default state as assumed, but is itself regulated in an unknown fashion. We discuss these findings and their implications for understanding pre‐patterning, digit regulation, and HH‐driven disease. (shrink)

There is a 'philosophers' assumption that there is a problem with the very notion of an unconscious mental state.The paper begins by outlining how the problem is generated, and proceeds to argue that certain conditions need to be fulfilled if the unconscious is to qualify as mental. An explanation is required as to why we would ever expect these conditions to be fulfilled, and it is suggested that the Freudian concept of repression has an essential role to play in such (...) an explanation. Notoriously this concept brings with it a further puzzle: it looks as though repression serves a purpose, and so requires an agent to execute this purpose, a repressor. Paradox is avoided only if repression is viewed in biologicalfunctional terms.The result is that the notion of the unconscious is saved from the a priori objections often levelled at it by philosophers.This still leaves considerable theoretical work to be done by psychological science. (shrink)

Plant‐specific NAC transcription factors (TFs) evolve during the transition from aquatic to terrestrial plant life and are amplified to become one of the biggest TF families. This is because they regulate genes involved in water conductance and cell support. They also control flower and fruit formation. The review presented here focuses on various properties, regulatory intricacies, and developmental roles of NAC family members. Processes controlled by NACs depend majorly on their transcriptional properties. NACs can function as both activators and/or (...) class='Hi'>repressors. Additionally, their homo/hetero dimerization abilities can also affect DNA binding and activation properties. The active protein levels are dependent on the regulatory cascades. Because NACs regulate both development and stress responses in plants, in‐depth knowledge about them has the potential to help guide future crop improvement studies. (shrink)

A study was carried out involving persons representing high-anxious, low-anxious and repressor types according to the classification of Weinberger, Davidson & Schwartz, selected using the Marlowe-Crowne Social Desirability Scale and the trait anxiety scale of the Spielberger State-Trait Anxiety Inventory. In seeking indicators of anxiety in repressors and high-anxious groups, the authors decided to analyse the level of dogmatism observed in utterance texts. The research was intended to determine whether styles of coping with threatening stimuli condition the level of (...) dogmatism, which was regarded as a cognitive defence mechanism against anxiety. The method of formal analysis of texts was used to identify their level of dogmatism, measured using the Dogmatism Quotient developed by Ertel. The highest value of the Dogmatism Quotient was recorded for repressors, and the lowest for the low-anxious subjects; a similar pattern was also observed for certain particular dimensions of dogmatism. Statistically significant differences in the level of dogmatism were found between the repressor and lowanxious groups and between the high-anxious and low-anxious groups. The study confirmed the previously discovered pattern whereby repressors exhibit more similarities to high-anxious than to low-anxious persons. (shrink)

Expression of most genes is regulated by the interaction of multiple transcription factors with cis‐regulatory sequences. Many studies have focused on how changes in promoters and enhancers alter gene expression and phenotype. Recently, Hare et al., using elegant wet and computational approaches uncovered a series of enhancers driving the expression of the even‐skipped gene in scavenger flies (Sepsidae).1 Despite the strong sequence divergence between the enhancers in sepsids and drosophilids, they lead to remarkably similar patterns of gene expression in transgenic (...) Drosophila embryos. This can be explained by the existence of intra‐enhancer compensatory mutations and the presence of overlapping/near binding sites for activators and repressors. BioEssays 30:1052–1057, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Gap genes stand at the top of the zygotic segmentation hierarchy in Drosophila. Their expression domains are set up by a combination of maternal regulatory signals and interactions among themselves. In addition, these regulatory pathways are partially redundantly specified by the maternal and zygotic genomes, or by multiple zygotic gene products. The gap genes code for transcription factors which exert their function by foming short‐range morphogenetic gradients; differential concentrations of these transcription factors can either act as activators or as (...) class='Hi'>repressors for the expression domains of neighbouring genes. It is possible to view the gap genes as a system of genes that subdivides the embryo by forming an activation‐repression cascade proceeding from anterior towards posterior. (shrink)

This essay is concerned with concentrations of entities, which play an important—albeit often overlooked—role in scientific explanation. First, I discuss an example from molecular biology to show that concentrations can play an irreducible causal role. Second, I provide a preliminary philosophical analysis of this causal role, suggesting some implications for extant theories of causation. I conclude by introducing the concept of causation by concentration, a form of statistical causation whose widespread presence throughout the sciences has been unduly neglected and which (...) deserves to be studied in more depth. 1 Introduction2 Solving Lillie's Paradox: Lysogenic Induction in Phage λ3 Repressor Concentration and the Tuning of the Switch4 Concentration and Causality5 Preemption in Concentrations: Analysis and Implications6 Causation by Concentration: General Definition, Refinements, and Further Applications. (shrink)

The present account spans the history of arginine regulation from its discovery in 1955 until the present. In 1957 I demonstrated that not only added arginine but also internally produced arginine represses enzyme formation and that the potential for enzyme synthesis is in excess of what is required for growth. In 1959 I located the regulatory gene argR encoding the arginine repressor. An unusual feature of this research was the finding that in E. coli B, in contrast to E. coli (...) K12, arginine synthesis is permanently repressed, independent of arginine. This was due to a single amino acid difference between the two repressors. Recent studies showed that, in natural populations of E. coli, K12‐type regulation is much more frequent than B‐type regulation, and that E. coli B evolved from a strain with K12‐type regulation. In competition experiments, E. coli K12 was found to be favored in the presence of arginine and E. coli B in its absence, showing that contrary to expectations permanently turned off regulation is favored over negative regulation in some environments. BioEssays 29:484–488, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

X‐chromosome inactivation refers to the coordinate regulation of almost all genes on the mammalian × chromosome. Most models for × chromosome inactivation suppose a role for methylation of × chromosome DNA sequences and/or the heterochromatinization of large «domains» of the × chromosome containing many genes.1 Some recent work concerning the expression of X‐linked transgenes, and parallels between regulated expression of sex‐linked genes in invertebrates and mammals, suggest that × chromosome inactivation may be a gene‐by‐gene event mediated by the interaction between (...) regulatory sequences common to all X‐linked genes and soluble activators and repressors. (shrink)

Possible etiological factors of congenital malformations as well as of human trisomies are considered in the framework of the repressor hypothesis. In this approach gene expression is envisaged from the point of view of the functional variations of the total activation energy for normal gene expression in homeostatic equilibrium. We restrict our attention to variations of the total activation energy under the effect of temperature gradients. We discuss the evidence that hyperthermia may be an etiological factor for trisomies in humans.

Heterochromatin remains condensed throughout the cell cycle, is generally transcriptionally inert and is built and maintainedbygroupsoffactors witheachgroupmember sharing a similar function. In mammals, these groups include sequence-specific transcriptional repressors, functionalRNAandproteinsinvolvedinDNAandhistone methylation. Heterochromatin is cemented together via interactions within and between each protein group and ismaintainedbythecell’sreplicationmachinery.Itcanbe constitutive (permanent) or facultative (developmentally regulated) and be any size, from a gene promotor to a whole genome. By studying the formation of facultative heterochromatin, we have gained information about how heterochromatin is assembled. We (...) have discovered that there are many different architectural plans for the building of heterochromatin, leading to a seemingly never-ending variety of heterochromatic loci, with each built according to a general rule. (shrink)