Histone variants are specialized histones which replace their canonical counterparts in specific nucleosomes. Together with histone post‐translational modifications and DNA methylation, they contribute to the epigenome. Histone variants are incorporated at specific locations by the concerted action of histone chaperones and ATP‐dependent chromatin remodelers. Recent studies have shown that the histone chaperone FACT plays key roles in preventing pervasive incorporation of two histone variants: H2A.Z and CenH3/CENP‐A. In addition, Spt6, another histone (...) class='Hi'>chaperone, was also shown to be important for appropriate H2A.Z localization. FACT and Spt6 are both associated with elongating RNA polymerase II. Based on these two examples, we propose that the establishment and maintenance of histone variant genomic distributions depend on a transcription‐coupled epigenome editing (or surveillance) function of histone chaperones. (shrink)

The mammalian egg employs a wide spectrum of epigenome modification machinery to reprogram the sperm nucleus shortly after fertilization. This event is required for transcriptional activation of the paternal/zygotic genome and progression through cleavage divisions. Reprogramming of paternal nuclei requires replacement of sperm protamines with canonical and non‐canonical histones, covalent modification of histone tails, and chemical modification of DNA (notably oxidative demethylation of methylated cytosines). In this essay we highlight the role maternal histone variants play during developmental reprogramming (...) following fertilization. We discuss how reduced maternal histone variant incorporation in somatic nuclear transfer experiments may explain the reduced viability of resulting embryos and how knowledge of repressive and activating maternal factors may be used to improve somatic cell reprogramming. (shrink)

In the cytoplasm of practically all living cells, potassium is the major cation while sodium dominates in the media (seawater, extracellular fluids). Both prokaryotes and eukaryotes have elaborate mechanisms and spend significant energy to maintain this asymmetric K+/Na+ distribution. This essay proposes an original line of evidence to explain how bacteria selected potassium at the very beginning of the evolutionary process and why it remains essential for eukaryotes.

Cancer cells accumulate widespread local and global chromatin changes and the source of this instability remains a key question. Here we hypothesize that chromatin alterations including unscheduled silencing can arise as a consequence of perturbed histone dynamics in response to replication stress. Chromatin organization is transiently disrupted during DNA replication and maintenance of epigenetic information thus relies on faithful restoration of chromatin on the new daughter strands. Acute replication stress challenges proper chromatin restoration by deregulating histone H3 lysine (...) 9 mono‐methylation on new histones and impairing parental histone recycling. This could facilitate stochastic epigenetic silencing by laying down repressive histone marks at sites of fork stalling. Deregulation of replication in response to oncogenes and other tumor‐promoting insults is recognized as a significant source of genome instability in cancer. We propose that replication stress not only presents a threat to genome stability, but also jeopardizes chromatin integrity and increases epigenetic plasticity during tumorigenesis. (shrink)

Depuis les années 1980, l’histoire de la médecine a connu un très fort renouvellement de ses approches, de ses objets et de sa mise en récit. L’histoire des femmes, du genre et des sexualités, en plein essor depuis ces mêmes années, a contribué de manière non négligeable à ce renouvellement en s’emparant de sources médicales délaissées par l’histoire de la médecine traditionnelle. En effet, durablement imprégnées par l’héritage positiviste du xixe siècle, l’histoire de la médecine et plus lar...

Durant les années 1950 et plus encore la décennie suivante, les ouvrages sur les questions féminines se multiplient. Cet article s’interroge sur les auteures de ces essais. Se dessine ainsi une génération d’expertes en études sur les femmes. Nées au début du siècle, profondément marquées par l’expérience de la deuxième guerre, ces nouvelles spécialistes sont diplômées des universités. Elles bénéficient de l’essor des médias mais ne parviennent pas toujours à avoir une situation professionnelle stable. Ensemble et s’appuyant sur les réflexions (...) beauvoiriennes, elles construisent un nouveau champ d’études, dont nous sommes les héritières. (shrink)

Yvonne Knibiehler continue son histoire des mères commencée il y a quelques années et arrêtée au seuil des ses propres enfantements, comme elle le rappelle dans l'introduction. L'entreprise n'est pourtant pas aisée. Non pas que le sujet déborderait trop sur l'intime de la chercheuse. L'égo-histoire, qui ne rime décidément pas avec l'histoire tout court, ne dépasse pas les premières pages de l'ouvrage. Mais le sujet est miné, piégé de l'intérieur par une charge idéologique hors du commu..

This article explores the critical reception of The Second Sex in France in 1949. Situating debates about the book in the context of the Cold War and the intellectual hegemony of existentialism, the author analyzes the main points of disagreement among different political factions—traditional Catholics, communists, members of the noncommunist left, and progressive Christians. She argues that the sexual questions Simone de Beauvoir raised in the public sphere fueled the primary points of contention.

Dès que Le Deuxième sexe de Simone de Beauvoir paraît en France en 1949, il est pris dans la division intellectuelle de la guerre froide. Mais est-ce le cas dans le reste de l’Europe à mesure que les traductions du livre paraissent? Une comparaison des réceptions et traductions du livre au cours de la guerre froide manque. Elle est pourtant rendue possible grâce à trois récents tournants historiographiques : la guerre froide au prisme du genre, l’étude des circulations transnationales du (...) Deuxième sexe et la traductologie féministe. (shrink)

Ce gros livre est le fruit d’un travail collectif, réalisé à l’initiative de l’Agence nationale de recherche sur le sida et les hépatites virales (ANRS), par un collectif de treize chercheur-e-s (sociologues, démographes, épidémiologistes, psycho-sociologues, économistes). Un long questionnaire a été élaboré et soumis par téléphone par soixante et un enquêteurs de l’Institut de sondage Ipsos à plus de 12 000 personnes âgées de 18 à 69 ans entre septembre 2005 et mars 2006. Cette enquête dite...

L'histoire des femmes depuis la Seconde Guerre mondiale est bien plus développée en Italie qu'en France. Le dernier ouvrage d'Anna Rossi-Doria nous en fournit une preuve supplémentaire. S'appuyant sur ses recherches personnelles, mais aussi sur une solide bibliographie, l'auteure s'interroge sur les multiples facettes du droit de vote féminin. Le décret qui institue le droit de vote féminin présente bien des similarités avec l'ordonnance française. Comme en France, celui-ci ne résulte..

Pour celles et ceux qui ne connaîtraient pas ou peu, ou mal Marie-France Brive, ce livre offre l'occasion de multiples rencontres émouvantes avec l'une des figures majeures de l'histoire des femmes en France. Car, comme son titre ne l'indique pas, cet ouvrage collectif est un hommage posthume. Ironie de l'histoire, le nom de celle qui affirmait : « il y a une construction de l'oubli des femmes en histoire » (p. 333) se trouve ainsi effacé de la couverture du livre (...) qui lui est consacré.... (shrink)

Sans prétendre faire œuvre exhaustive ni même définitive, Mariette Sineau et Evelyne Tardy se livrent à un instructif travail comparatif sur le droit des femmes dans les deux territoires francophones. Malgré toutes leurs différences, ceux-ci se montrent suffisamment proches pour soutenir la comparaison. Tous deux adoptent le code civil napoléonien (en 1866 pour le Québec pourtant cerné par la bien plus progressive common law), tous deux sont également à forte dominante catholique. Le m..

L'ouvrage de William Guéraiche s'inscrit dans un renouvellement notable de l'historiographie de ces quelques dernières années. L'après-Deuxième Guerre mondiale, les années cinquante se voient revisitées de multiples façons par les travaux de Noël Burch et Geneviève Sellier, Luc Capdevila, Fabrice Virgili et moi-même. Le découpage chronologique de l'étude ne suit pas les coupures majeures de l'histoire politique française; ni 1958 ni 1968 ne fondent de ruptures, par exemple. La superpos...

Cet ouvrage reprend sous forme remaniée les actes du colloque « Germaine Poinso-Chapuis, témoin de son temps » organisé à Marseille par l'association Les Femmes et la Ville (20-22 novembre 1997). Il répare heureusement l'oubli injuste d'une figure majeure de l'histoire de l'après-guerre. Moins connue que les femmes sous-secrétaires d'État du Front populaire alors qu'elle est la première femme ministre de plein exercice, moins populaire que Simone Veil alors qu'elle a été députée pendan...

Exceptionnel, l'itinéraire politique de Marcelle Devaud, l'est assurément. Sénatrice dès 1946 puis députée (de 1958 à 1962), maire de Colombes (1959-1965), membre de Conseil Economique et Social (1962-1979), représentante de la France à la commission de la femme aux Nations-Unies (1975-1983), elle cumule tous ces mandats avec de nombreuses responsabilités dans les associations féminines, dont plusieurs fondées par elle-même. Quand on sait qu'elle est par ailleurs mère de 6 enfants, on ..

Résumé Michèle Le Dœuff est une philosophe qui a beaucoup contribué aux études beauvoiriennes, mais dont l’ apport a été sous-évalué. Pourtant, Le Dœuff a été la première à faire un travail critique, philosophique et féministe autour du Deuxième Sexe, d’ abord dans son célèbre article « Cheveux longs, idées courtes » (1977), puis de façon plus approfondie dans L’ Étude et le rouet (1989). Les études beauvoiriennes ont sans doute encore beaucoup à puiser dans l’ œuvre de Le Dœuff.

Molecular chaperones assist de novo protein folding and facilitate the refolding of stress‐denatured proteins. The molecular chaperone concept was coined nearly 35 years ago, and since then, tremendous strides have been made in understanding how these factors support protein folding. Here, we focus on how various chaperone proteins were first identified to play roles in protein folding. Examples are used to illustrate traditional routes of chaperone discovery and point out their advantages and limitations. Recent advances, including the (...) development of folding biosensors and promising methods for the stabilization of proteins in vivo, provide new routes for chaperone discovery. (shrink)

We propose for the first time to divide histone proteolysis into “histone degradation” and the epigenetically connoted “histone clipping”. Our initial observation is that these two different classes are very hard to distinguish both experimentally and biologically, because they can both be mediated by the same enzymes. Since the first report decades ago, proteolysis has been found in a broad spectrum of eukaryotic organisms. However, the authors often not clearly distinguish or determine whether degradation or clipping was (...) studied. Given the importance of histone modifications in epigenetic regulation we further elaborate on the different ways in which histone proteolysis could play a role in epigenetics. Finally, unanticipated histone proteolysis has probably left a mark on many studies of histones in the past. In conclusion, we emphasize the significance of reviving the study of histone proteolysis both from a biological and an experimental perspective.Also watch the Video Abstract. (shrink)

Histone deacetylase inhibitors (HDACi) are in clinical trials against a variety of cancers. Despite early successes, results against the more common solid tumors have been mixed. How is it that so many cancers, and most normal cells, tolerate the disruption caused by HDACi‐induced protein hyperacetylation? And why are a few cancers so sensitive? Here we discuss recent results showing that human cells mount a coordinated transcriptional response to HDACi that mitigates their toxic effects. We present a hypothetical signaling system (...) that could trigger and mediate this response. To account for the existence of such a response, we note that HDACi of various chemical types are made by a variety of organisms to kill or suppress competitors. We suggest that the resistance response in human cells is a necessary evolutionary consequence of exposure to environmental HDACi. We speculate that cancers sensitive to HDACi are those in which the resistance response has been compromised by mutation. Identifying such mutations will allow targeting of HDACi therapy to potentially susceptible cancers. (shrink)

Self‐renewal and differentiation of stem cells are tightly regulated processes subject to intrinsic and extrinsic signals. Molecular chaperones and co‐chaperones, especially heat shock proteins (Hsp), are ubiquitous molecules involved in the modulation of protein conformational and complexation states. The function of Hsp, which are typically associated with stress response and tolerance, is well characterized in differentiated cells, while their role in stem cells remains unclear. It appears that embryonic stem cells exhibit increased stress tolerance and concomitant high levels of (...) class='Hi'>chaperone expression. This review critically evaluates stem cell research from a molecular chaperone perspective. Furthermore, we propose a model of chaperone‐modulated self‐renewal in mouse embryonic stem cells. (shrink)

Expression of sexually dimorphic behaviors critical for reproduction depends on the organizational actions of steroid hormones on the developing brain. We offer the new hypothesis that transcriptional activities in brain regions executing these sexually dimorphic behaviors are modulated by estrogen‐induced modifications of histone proteins. Specifically, in preoptic nerve cells responsible for facilitating male sexual behavior in rodents, gene expression is fostered by increased histone acetylation and reduced methylation (Me), and, that the opposite set of histone modifications will (...) be found in females. Conversely, in ventromedial hypothalamic neurons that are responsible for coordinating female sexual behavior, transcriptional activities in genetic females are fostered by increased histone acetylation and reduced Me, and, further, that the opposite set of histone modifications will be found in males. Thus, these epigenetic events will guarantee that effects of sex hormone exposure during the neonatal critical period will be translated into lasting sex differences in adult reproductive behaviors. (shrink)

Histone acetylation is an important regulatory mechanism that controls transcription and diverse nuclear processes. While great progress has been made in understanding how localized acetylation and deacetylation control promoter activity, virtually nothing is known about the consequences of acetylation throughout entire chromosomal regions. An increasing number of genes have been found to reside in large chromatin domains that are controlled by regulatory elements many kilobases away. Recent studies have shown that broad histone acetylation patterns are hallmarks of chromatin (...) domains. The purpose of this review is to discuss how such patterns are established and their implications for regulating gene expression. BioEssays 23:820–830, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

The haploid male germ cell differentiation program controls essential steps of male gametogenesis and relies partly on a significant number of sex chromosome‐linked genes. These genes need to escape chromosome‐wide transcriptional repression of sex chromosomes, which occurs during meiosis and is largely maintained in post‐meiotic cells. A newly discovered histone lysine modification, crotonylation (Kcr), marks X/Y‐linked genes that are active in post‐meiotic male germ cells. Histone Kcr, by conferring resistance to transcriptional repressors, could be a dominant element in (...) maintaining these genes active in the globally repressive environment of haploid cell sex chromosomes. Furthermore, the same mark was found associated with post‐meiotically activated genes on autosomes. Histone Kcr therefore appears to be an indicator of the male haploid cell gene expression program and a notable element of genome programming in the post‐meiotic phases of spermatogenesis. (shrink)

Fibrillar protein aggregates are the pathological hallmark of a group of age‐dependent neurodegenerative conditions, including Alzheimer's and Parkinson's disease. Aggregates of the microtubule‐associated protein Tau are observed in Alzheimer's disease and primary tauopathies. Tau pathology propagates from cell to cell in a prion‐like process that is likely subject to modulation by extracellular chaperones such as Clusterin. We recently reported that Clusterin delayed Tau fibril formation but enhanced the activity of Tau oligomers to seed aggregation of endogenous Tau in a cellular (...) model. In contrast, Clusterin inhibited the propagation of α‐Synuclein aggregates associated with Parkinson's disease. These findings raise the possibility of a mechanistic link between Clusterin upregulation observed in Alzheimer's disease and the progression of Tau pathology. Here we review the diverse functions of Clusterin in the pathogenesis of neurodegenerative diseases, focusing on evidence that Clusterin may act either as a suppressor or enhancer of pathology. (shrink)

We highlight a recent study exploring the hand‐off of UV damage to several key nucleotide excision repair (NER) proteins in the cascade: UV‐DDB, XPC and TFIIH. The delicate dance of DNA repair proteins is choreographed by the dynamic hand‐off of DNA damage from one recognition complex to another damage verification protein or set of proteins. These DNA transactions on chromatin are strictly chaperoned by post‐translational modifications (PTM). This new study examines the role that ubiquitylation and subsequent DDB2 degradation has during (...) this process. In total, this study suggests an intricate cellular timer mechanism that under normal conditions DDB2 helps recruit and ubiquitylate XPC, stabilizing XPC at damaged sites. If DDB2 persists at damaged sites too long, it is turned over by auto‐ubiquitylation and removed from DNA by the action of VCP/p97 for degradation in the 26S proteosome. (shrink)

Background: Medical chaperones (MC) are underutilised. The influence of Islamic culture on the use of MC is not known. Aim: To examine physicians’ use and perception of MC in Islamic culture. Setting: A major tertiary care hospital in Saudi Arabia. Methods: 315 self-administered questionnaires were distributed to attendees of grand rounds of 13 departments. Results: 186 (59%) questionnaires were completed. 64.5% of the respondents were 30–49 years old, 75.8% were men and 31.2% were in training; 79% had a clinic load (...) of under 50 patients per week and 47.8% had postgraduate training (PGT) in an Islamic country. MC were reported to be infrequently (⩽25% of the time) used by 44.1% (69.2% female vs 39% male physicians, p = 0.001; 58.6% in training vs 36.8% attending, p = 0.007; 52.1% PGT in Islamic vs 35.6% in western countries, p = 0.027), offered by 52.7% (78.9% female vs 46.8% male physicians, p<0.001) and requested by 79% of patients. MC were reported to be commonly (>75% of the time) used, offered by physicians and requested by patients by 38.2%, 29% and 7.5% of respondents, respectively. The most frequently cited reasons for not using MC were privacy/confidentiality (36.6%) and understaffing (30.5%). Equal numbers of respondents perceived MC use as a protection for physicians or patients (67.7% and 65.6%, respectively). Conclusions: MC are underutilised even in Islamic culture, especially among female physicians. Training in western countries is favourably associated with MC use. Underutilisation appears to be related to privacy/confidentiality, understaffing and failure of patients to request a MC. (shrink)

The model of DNA-histones has the following elements: The hydrogen bonds between the complementary nucleotide bases function as informational gates. When the electrons π of one nucleotide base are excited, an exchange of protons is produced between the two complementary bases. The result is the displacement of the conjugated double bonds which facilitates the inter-molecular transmission of the electronic wave of excitation by electro-magnetic coupling. Each triplet of nucleotide bases of DNA fixes one definite amino acid . Between the nucleotide (...) bases and the amino acids there are constituted informational gates, which ensure the circulation of the electronic wave of excitation. An input signal molecule arrives at the receiver gene and unleashes the activity of the enzymes which introduce in the DNA-histones system the electronic wave of excitation. The electronic wave of excitation arises as a result of the break of the high-energy bonds of ATP. Then, the electronic excitation is transmitted to the productor gene where it represents the signal for starting the synthesis of the mRNA.Le modèle de système ADN-Histone a les éléments suivants: Les liaisons d'hydrogène entre les bases nucléotidiques complémentaires fonctionnent comme des portes informationnelles. Quand les électrons π d'une base nucléotidique sont excités, il se produit un échange de protons entre les bases complémentaires. Le résultat est un déplacement des doubles liaisons conjugées qui facilite la transmission de l'onde d'excitation électronique par un couplage électromagnétique. Chaque triplet de bases nucléotidiques de l'ADN fixe un certain amino-acide . Entre les bases nucléodiques et les amino-acides se constituent des portes informationnelles qui assurent la circulation de l'onde d'excitation dlectronique. Une molécule signal d'entrée arrive au gène récepteur et déclenche l'activité des enzymes qui introduisent dans le système ADN-histone l'excitation électronique. L'excitation électronique apparait comme résultat de la rupture des liaisons de haute énergie del' ATP. l'Onde d'excitation électronique est transmise au gène producteur, où elle rdprésente le signal pour faire commencer la synthèse de l'ARNm.Das Modell des DNS-Histonen Systems weist folgende Elemente auf: Die Wasserstoffbindungen zwischen den komplementäaren Nukleotidbasen funktionieren wie informationale Pforten. Wenn die π Elektronen einer Nukleotidbase erregt werden, ensteht ein Protonenwechsel zwischen den Komplementären Basen. Das Ergebnis ist eine Verschiebung der konjugierten Doppelbindungen, die die Weiterleitung der elektronischen Erregungswelle durch eine elektromagnetische Kupplung erleichtert. Jedes Nukleotidbasentriplett der DNS fixiert eine bestimmte Aminosäure . Zwischen den Nukelotidbasen und den Aminosäuren entstehen Informationspforten, welche den Umlauf der elektronischen Erregungswelle sichern. Ein Eintrittsignal Moleküul gelangt zur Rezeptorgen und löst die Aktivität von Enzymen aus, welche die elektronische Erregungswelle in das DNS-Histonen System einführen werden. Die elektronische Erregungswelle erscheint als Ergebnis der Spaltung der hochenergetischen Bindungen des ATP-s. Die elektronische Erregungswelle wird alsdann zur Produktorgen weitergeleitet, wo sie das Signal zum Beginn der Synthese der mRNS darstellt. (shrink)

Histone acetylation has been recognized as an important post‐translational modification of core nucleosomal histones that changes access to the chromatin to allow gene transcription, DNA replication, and repair. Histone acetyltransferases were initially identified as co‐activators that link DNA‐binding transcription factors to the general transcriptional machinery. Over the years, more chromatin‐binding modes have been discovered suggesting direct interaction of histone acetyltransferases and their protein complex partners with histone proteins. While much progress has been made in characterizing (...) class='Hi'>histone acetyltransferase complexes biochemically, cell‐free activity assay results are often at odds with in‐cell histone acetyltransferase activities. In‐cell studies suggest specific histone lysine targets, but broad recruitment modes, apparently not relying on specific DNA sequences, but on chromatin of a specific functional state. Here we review the evidence for general versus specific roles of individual nuclear lysine acetyltransferases in light of in vivo and in vitro data in the mammalian system. (shrink)

Immunofluorescent labelling demonstrates that human metaphase chromosomes contain hyperacetylated histone H4. With the exception of the inactive X chromosome in female cells, where the bulk of histone H4 is under‐acetylated, H4 hyperacetylation is non‐uniformly distributed along the chromosomes and clustered in cytologically resolvable chromatin domains that correspond, in general, with the R‐bands of conventional staining. The strongest immunolabelling is often found in T‐bands, the subset of intense R‐bands having the highest GC content. The majority of mapped genes also (...) occurs in R‐band regions, with the highest gene density in T‐bands. These observations are consistent with a model in which hyperacetylation of histone H4 marks the position of potentially active gene sequences on metaphase chromosomes. Since acetylation is maintained during mitosis, progeny cells receive an imprint of the histone H4 acetylation pattern that was present on the parental chromosomes before cell division. Histone acetylation could provide a mechanism for propagating cell memory, defined as the maintenance of committed states of gene expression through cell lineages. (shrink)

In postmitotic neurons, nucleosomal turnover was long considered to be a static process that is inconsequential to transcription. However, our recent studies in human and rodent brain indicate that replication‐independent (RI) nucleosomal turnover, which requires the histone variant H3.3, is dynamic throughout life and is necessary for activity‐dependent gene expression, synaptic connectivity, and cognition. H3.3 turnover also facilitates cellular lineage specification and plays a role in suppressing the expression of heterochromatic repetitive elements, including mutagenic transposable sequences, in mouse embryonic (...) stem cells. In this essay, we review mechanisms and functions for RI nucleosomal turnover in brain and present the hypothesis that defects in histone dynamics may represent a common mechanism underlying neurological aging and disease. -/- . (shrink)

Polycomb group proteins are evolutionary conserved chromatin‐modifying complexes, essential for the regulation of developmental and cell‐identity genes. Polycomb‐mediated transcriptional regulation is provided by two multi‐protein complexes known as Polycomb repressive complex 1 (PRC1) and 2 (PRC2). Recent studies positioned PRC1 as a foremost executer of Polycomb‐mediated transcriptional control. Mammalian PRC1 complexes can form multiple sub‐complexes that vary in their core and accessory subunit composition, leading to fascinating and diverse transcriptional regulatory mechanisms employed by PRC1 complexes. These mechanisms include PRC1‐catalytic activity (...) toward monoubiquitination of histone H2AK119, a well‐established hallmark of PRC1 complexes, whose importance has been long debated. In this review, the central roles that PRC1‐catalytic activity plays in transcriptional repression are emphasized and the recent evidence supporting a role for PRC1 complexes in gene activation is discussed. (shrink)

The discovery of “molecular chaperones” has dramatically changed our concept of cellular protein folding. Rather than folding spontaneously, most newly synthesized polypeptide chains seem to acquire their native conformation in a reaction mediated by these versatile helper proteins. Understanding the structure and function of molecular chaperones is likely to yield useful applications for medicine and biotechnology in the future.

Histones occur in equal amounts to DNA in the cell nucleus and are largely responsible for the compaction of the genome into chromatin via the formation of nucleosomes and higher‐order structures. Whereas two of the five histone types exhibit little structural variation, the remaining three occur in many variant tissue‐ or species‐specific forms. Multiple postsynthetic enzymatic modifications accompanying virtually any type of genome activity, together with the programmed appearance of many histone variants during sea urchin embryogenesis (and other (...) differentiation events in a number of organisms) make histones a challenging enigma in eukaryotic molecular biology. (shrink)

Histone post-translational modifications play important roles in transcriptional regulation. It is known that multiple histone modifications can act in a combinatorial manner. In this study, we investigated the effects of multiple histone modifications on expression levels of five gene categories in coding regions. The combinatorial patterns of modifications for the five gene categories were also studied in the regions. Our results indicated that the differences in the expression levels between any two gene categories were significant. There were (...) some corresponding differences in multiple histone modification levels among the five gene categories. Multiple histone modifications jointly impacted expression levels of every gene category. Four mutual combinations of histone modifications were found and analyzed. (shrink)

In this paper I use a case study—the discovery of the chaperon function exerted by proteins in the various steps of the hereditary process—to re-discuss the question whether the nucleic acids are the sole repositories of relevant information as assumed in the information theory of heredity. The evidence I here present of a crucial role for molecular chaperones in the folding of nascent proteins, as well as in DNA duplication, RNA folding and gene control, suggests that the family of proteins (...) acting as molecular chaperones provides information that is complementary to that stored in the nucleic acids, and equally important. A re-evaluation of the role of proteins in the hereditary process is in order away from the gene-centric approach of the information theory of heredity, to which neo-Darwinian evolutionists adhere. (shrink)

Le mot sexologie, la science de la sexualité, apparaît en France au début des années 1910. Il marque, de la part de ceux qui en usent, la volonté à la fois de lutter pour l’égalité des droits en matière de pratiques sexuelles et de rompre avec le savoir médical sur la sexualité. Dans son livre Les origines de la sexologie, 1850-1900, Sylvie Chaperon explore ce champ nouveau de l’histoire et se propose de démêler les fils qui, en ce domaine, enchevêtrent (...) si fortement savoir, pouvoir et représe... (shrink)

The N‐terminal domain of histone H4 has been implicated in various nuclear functions, including gene silencing and activation and replication‐linked chromatin assembly. Many of these have been identified by using H4 mutants in the yeast S. cerevisiae. In a recent paper, Megee et al.(1) use this approach to show that mutants in which all four N‐terminal H4 lysines are substituted with glutamines accumulate increased levels of DNA damage. A single lysine, but not an arginine, anywhere in the N‐terminal domain (...) suppresses this phenotype. It is suggested that histone H4 plays a role in maintaining genome integrity through the cell cycle, possibly by a mechanism involving lysine acetylation. (shrink)

Post-translational histone modifications and their biological effects have been described as a ‘histone code’. Independently, Barbieri used the term ‘organic code’ to describe biological codes in addition to the genetic code. He also provided the defining criteria for an organic code, but to date the histone code has not been tested against these criteria. This paper therefore investigates whether the histone code is a bona fide organic code. After introducing the use of the term ‘code’ in (...) biology, the criteria a putative organic code such as the histone code must conform to in order to be recognised as an organic code are described. Our current knowledge of histones and their major post-translational modifications, and the specific protein binding domains that recognise and translate these into specific biological effects, is then reviewed in detail. The histone modification system is then placed in the context of an organic code and it is concluded that it fulfils all the requirements of an organic code. The marks produced on histones by processes such as acetylation and methylation act as organic signs that are translated into unique biological effects, their biological meanings. These translations are accomplished by effector proteins that consist of a binding domain that recognises a specific histone mark and a regulatory domain that mediates the biological effect. Crucially, these domains can be experimentally interchanged between different effector proteins, thus altering the rules that specify the relationships between sign and meaning. The effector proteins therefore fulfil the role of adaptor molecules. (shrink)

Cet ouvrage comble un vide dans l'histoire des femmes et du féminisme, qui ne s'était guère intéressée jusqu'ici à la période qui va de 1945 à 1970, à l'exception de travaux comme ceux de Dominique Loiseau sur le militantisme des femmes à Nantes ou notre recherche commune ­ Michelle Zancarini-Fournel et moi-même ­ sur des parcours de femmes à Saint-Étienne, incluant les années 1950. Grâce à ce livre, nous disposons maintenant, d'une bibliographie assez complète sur le féminisme françai...

Histone modifications play a critical role in the control over activities of the eukaryotic genome; among these chemical alterations, the methylation of lysine K9 in histone H3 (H3K9) is one of the most extensively studied. The number of enzymes capable of methylating H3K9 varies greatly across different organisms: in fission yeast, only one such methyltransferase is present, whereas in mammals, 10 are known. If there are several such enzymes, each of them must have some specific function, and they (...) can interact with one another. Thus arises a complex system of interchangeability, “division of labor,” and contacts with each other and with diverse proteins. Histone methyltransferases specialize in the number of methyl groups that they attach and have different intracellular localizations as well as different distributions on chromosomes. Each also shows distinct binding to different types of sequences and has a specific set of nonhistone substrates. (shrink)