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Fetal myogenesis represents a critical period of porcine skeletal muscle development and requires coordinated expression of thousands of genes. Epigenetic mechanisms, including DNA methylation, drive transcriptional regulation during development; however, these processes are understudied in developing porcine tissues. We performed bisulfite sequencing to assess DNA methylation in pig longissimus dorsi muscle at 41- and 70-days gestation (dg), as well as RNA- and small RNA-sequencing to identify coordinated changes in methylation and expression between myogenic stages. We identified 45 739 differentially methylated regions (DMRs) between stages, and the majority (N = 34 232) were hypomethylated at 70 versus 41 dg. Integration of methylation and transcriptomic data revealed strong associations between differential gene methylation and expression. Differential miRNA methylation was significantly negatively correlated with abundance, and dynamic expression of assayed miRNAs persisted postnatally Motif analysis revealed significant enrichment of myogenic regulatory factor motifs among hypomethylated regions, suggesting that DNA hypomethylation may function to increase accessibility of muscle-specific transcription factors. We show that developmental DMRs are enriched for GWAS SNPs for muscle- and meat-related traits, demonstrating the potential for epigenetic processes to influence phenotypic diversity. Our results enhance understanding of DNA methylation dynamics of porcine myogenesis and reveal putative cis-regulatory elements governed by epigenetic processes. Key words: DNA methylation, pig, longissimus dorsi muscle, microRNA, WGBS, Introduction Skeletal muscle accounts for the majority of carcass weight in pigs and other livestock species, and its physiology influences numerous meat quality phenotypes (England et al. 2013). Fetal myogenesis [...]

Near-isogenic lines (NILs) are classical genetic tools used to dissect the actions of an allele when placed in a uniform genetic background. Although the goal of NIL creation is to examine the effects of a single allele in isolation, DNA linked to the allele is invariably retained and can confound any allele-specific effects. In addition to genetic variation, highly polymorphic species such as Zea mays will contain introgressed polymorphisms encompassing transposable elements (TEs) and the cis-acting small RNA (sRNA) that represses them. Through transcriptomics, we described the differences in sRNA and TE transcriptional expression between a W22-derived introgression and its homologous B73 region. As anticipated, many differences in sRNA expression were observed. Unexpectedly, however, 24nt sRNA expression over the introgressed region was low overall compared to both the homologous B73 region and the rest of the genome. Across the introgression, low sRNA expression was accompanied by increased TE transcription. Possible explanations for the observed trends in sRNA and TE expression across the introgression region are discussed. These findings support the notion that any introgressed allele is in an epigenetic environment distinct from that found at the allele from the recurrent parent. Additionally, these results suggest that further study of sRNA expression levels during the introgression process is warranted. Key words: small RNA, transcriptomics, epigenetics, near-isogenic lines, Zea mays. Les lignees quasi-isogeniques (NIL pour <>) constituent un outil genetique classique pour dissequer l'effet d'un allele lorsqu'il se trouve dans un fond genetique uniforme. Bien que le but de la creation des NIL soit d'examiner les effets d'un seul allele isolement, l'ADN bordant cet allele est inevitablement preserve et peut affecter l'effet de tout allele specifique. En plus de la variation genetique, les especes tres polymorphes comme Zea mays vont avoir des polymorphismes introgresses incluant des elements transposables (TE) et de petits ARN (sRNA) agissant en cis pour les reprimer. Via une approche transcriptomique, les auteurs decrivent les differences d'expression transcriptionnelle des sRNA et des TE entre une introgression derivee de W22 et la region homologue chez B73. Tel qu'anticipe, plusieurs differences d'expression des sRNA ont ete observees. Etonnamment, l'expression des genes codant les sRNA de 24nt situes dans la region introgressee etait faible globalement par rapport a la region homologue chez B73 et le reste du genome. Sur l'ensemble de la zone introgressee, la faible abondance des sRNA etait accompagnee d'une transcription accrue des TE. Les auteurs discutent de possibles explications pour les tendances observees en matiere d'expression des sRNA et des TE au sein de la zone introgressee. Ces observations supportent la notion que tout allele introgresse loge dans un environnement epigenetique distinct de celui dans lequel se trouve l'allele au sein du parent recurrent. De plus, ces resultats suggerent que des etudes plus approfondies sont necessaires pour caracteriser les niveaux d'expression des sRNA au cours du processus d'introgression. [Traduit par la Redaction] Mots-cles : petits ARN, transcriptomique, epigenetique, lignees quasi-isogeniques, Zea mays., Introduction Classical genetic experiments and breeding practices use crosses between diverse parents to dissect the constituents of different phenotypes. Once an allele of interest is identified, it can be integrated [...]

The COVID-19 pandemic is one of the most significant public health threats in recent history and has impacted the lives of almost everyone worldwide. Epigenetic mechanisms contribute to many aspects of the SARS-CoV-2 replication cycle, including expression levels of viral receptor ACE2, expression of cytokine genes as part of the host immune response, and the implication of various histone modifications in several aspects of COVID-19. SARS-CoV-2 proteins physically associate with many different host proteins over the course of infection, and notably there are several interactions between viral proteins and epigenetic enzymes such as HDACs and bromodomain-containing proteins as shown by correlation-based studies. The many contributions of epigenetic mechanisms to the viral life cycle and the host immune response to infection have resulted in epigenetic factors being identified as emerging biomarkers for COVID-19, and project epigenetic modifiers as promising therapeutic targets to combat COVID-19. This review article highlights the major epigenetic pathways at play during COVID-19 disease and discusses ongoing clinical trials that will hopefully contribute to slowing the spread of SARS-CoV-2. Key words: epigenetics, COVID-19, ACE2, DNA methylation, histone modifications, clinical trials. La pandemie de la COVID-19 constitue l'une des plus importantes menaces a la sante publique de l'histoire recente et a touche les vies de presque tous a l'echelle planetaire. Des mecanismes epigenetiques contribuent a plusieurs aspects du cycle de replication du SRAS-CoV-2, incluant le niveau d'expression du recepteur viral ACE2, l'expression des genes codant pour les cytokines qui participent a la reponse immuni-tairedel'hote, et l'implication de plusieurs modifications des histones touchant de nombreux aspects de la COVID-19. Les proteines du SRAS-CoV-2 se lient physiquement avec plusieurs proteines de l'hote au cours de l'infection et, notamment, des etudes de correlation ont revele de nombreuses interactions entre des proteines virales et des enzymes epigenetiques telles que les HDAC et des proteines a bromodomaine. Les nombreuses contributions des mecanismes epigenetiques dans le cycle vital du virus et dans la reponse immunitaire de l'hote ont fait en sorte que les facteurs epigenetiques sont vus comme etant des biomarqueurs emergents pour la COVID-19 et laissent entrevoir que des modificateurs epigenetiques pourraient constituer des cibles therapeutiques interes-santes pour combattre la COVID-19. Cet article de synthese met en lumiere les principaux sentiers epigenetiques qui jouent un role dans la maladie de la COVID-19 et les auteurs discutent des essais cliniques en cours qui con-tribueront possiblement a ralentir la propagation du SRAS-CoV-2. [Traduit par la Redaction] Mots-cles: epigenetique, COVID-19, ACE2, methylation de l'ADN, modifications des histones, essais cliniques., Introduction Epigenetic modifications, such as DNA methylation and post-translational modifications of histone tails, contribute to the regulation of almost all biological processes, and are also involved in many different human [...]

Translating to the Community (T2C) is a social biorepository designed to advance new diagnostic tools and realign community--clinical processes, with the aim to mitigate the short- and long-term impacts of fetal alcohol spectrum disorder (FASD) as well as prenatal alcohol exposure and its co-morbidities and behaviors. In this paper, we describe the evolution of this repository as a new translational partnership to advance a precision-medicine approach to FASD. Key to its evolution was a partnership between academic researchers, Indigenous communities, families, and a regional diagnostic clinic. We further describe the rationale for social biobanking, the type of banking, ethical engagement of families, communities, and clinics, their roles in repository design, governance, translation, and research activities, types of data collected from families, and how the study data are managed, reported, and accessed. The repository design includes biological samples, social-contextual healthsurvey data, and clinical data (which are linkable to administrative data) from community and clinical cohorts of diagnosed children, children prenatally exposed but not diagnosed, children suspected to have had a prenatal exposure, and related siblings, biological parents, and unrelated children and their parents. From these cohorts and families, potential studies drawing on this data will shed light on various risk factors, social and biological pathways, and service utilization issues, with the aim to implement primary and secondary prevention and intervention strategies. Key words: fetal alcohol spectrum disorder, social genomic biorepository, translational studies, community and family participation, Indigenous, ethics and governance. << Translating to the Community (T2C) >> (Transfert a la communaute) est un bio-referentiel social concu pour faire progresser le developpement de nouveaux outils diagnostiques et realigner la communaute et les processus cliniques, dans le but d'attenuer les impacts a court et long termes des troubles du spectre de l'alcoolisation foetale (TSAF), de l'exposition prenatale a l'alcool, de leurs comorbidites et des comportements qui leur sont associes. Dans cet article, les auteurs decrivent l'evolution de cereferentiel comme nouvel outil departenariat translationnel afin de promouvoir une approche de medecine de precision dans les TSAF. L'element cle de cette evolution a ete un partenariat entre les chercheurs universitaires, les communautes autochtones, les familles et une clinique regionale de diagnostic. Ils decrivent plus en detail les raisons d'etablir une bio-banque sociale, le type de stockage, l'engagement ethique des familles, des communautes et des cliniques, leur role dans la conception et la gouvernance du referentiel, ainsi que dans les activites de recherche et de transfert realisees, les types de donnees recueillies des familles et comment ces donnees d'etudes sont gerees, rapportees et rendues accessibles. Comme il a ete concu, le referentiel comprend des echantillons biologiques, des donnees d'enquetes sociales, contextuelles et de sante, ainsi que des donnees cliniques (qui peuvent etre correlees aux donnees administratives) a partir des cohortes des communautes et cliniques d'enfants diagnostiques, d'enfants exposes a l'alcool durant la periode prenatale mais non diagnostiques, d'enfants que l'on croit avoir ete exposes a l'alcool durant la periode prenatale et leurs freres et soeurs, leurs parents biologiques, des enfants non apparentes et leurs parents. A partir de ces cohortes et des familles, les etudes potentielles s'appuyant sur ces donnees feront la lumiere sur differents facteurs de risque, les parcours sociaux et biologiques, et les problematiques d'utilisation des services, dans le but de mettre en oeuvre des strategies de prevention et d'intervention primaires et secondaires. [Traduit par la Redaction] Mots-cles : troubles du spectre de l'alcoolisation foetale, bio-referentiel social, etudes translationnelles, participation des communautes et des familles, Autochtone, ethique et gouvernance., Introduction Globally, fetal alcohol spectrum disorder (FASD), a result of a prenatal exposure to alcohol (prenatal alcohol exposure; PAE), is the most common neurodevelopmental condition, exceeding 1% worldwide with an [...]

This paper discusses the current state of knowledge and practice for diagnosing fetal alcohol spectrum disorder (FASD). The strengths and challenges of different models of diagnosis are compared. Some models require a team approach for evaluation, while other approaches assume that a clinician in his or her office provides a diagnosis based on a review of the patient's medical and social history, behaviour, and physical examination. The author reviews the emergence of new information from recent advances in genetics, imaging, and electrophysiology that has the potential to lead to changes in practice and improved reliability of an FASD diagnosis. Key words: guidelines, multidisciplinary team, imaging, genetics, epigenetics. Cet article presente l'etat actuel des connaissances et des pratiques relatives au diagnostic des troubles du spectre de l'alcoolisation foetale (TSAF). Les forces et les defis des differents modeles de diagnostic sont compares. Quelques modeles requierent une approche par equipe, alors que d'autres assument qu'un clinicien ou une clinicienne dans son bureau peut poser un diagnostic sur la base de la synthese de l'historique medicale et sociale de la patiente, de ses comportements et de l'examen physique. L'auteur passe en revue l'emergence d'une nouvelle information tiree des progres recents sur le plan de la genetique, de l'imagerie et de l'electrophysiologie, qui ont le potentiel de mener a des changements dans les pratiques et a des ameliorations dans la fiabilite du diagnostic des TSAF. [Traduit par la Redaction] Mots-cles : lignes directrices, equipe multidisciplinaire, imagerie, genetique, epigenetique., Introduction and history Since the first published description of the role of alcohol in adverse outcomes in children almost 50 years ago (Lemoine et al. 1968; Jones et al. 1973), [...]

In western countries, alcohol consumption is widespread in women of reproductive age, and in binge quantities. These countries also continue to have high incidences of unplanned pregnancies, with women often reported to cease drinking after discovering their pregnancy. This suggests the early embryo may be highly exposed to the detrimental effects of alcohol during the periconception period. The periconception and pre-implantation windows, which include maturation of the oocyte, fertilisation, and morphogenesis of the pre-implantation embryo, are particularly sensitive times of development. Within the oviduct and uterus, the embryo is exposed to a unique nutritional environment to facilitate its development and establish de-novo expression of the genome through epigenetic reprogramming. Alcohol has wide-ranging effects on cellular stress, as well as hormonal, and nutrient signalling pathways, which may affect the development and metabolism of the early embryo. In this review, we summarise the adverse developmental outcomes of early exposure to alcohol (prior to implantation in animal models) and discuss the potential mechanisms for these outcomes that may occur within the protected oviductal and uterine environment. One interesting candidate is reduced retinoic acid synthesis, as it is implicated in the control of epigenetic reprogramming and cell lineage commitment, processes that have adverse consequences for the formation of the placenta, and subsequently, fetal programming. Key words: ethanol, programming, embryo, epigenetics, retinoic acid. Dans les pays occidentaux, la consommation d'alcool en quantite excessive est repandue chez les femmes en age de procreer. Ces pays continuent aussi de presenter une haute incidence de grossesses non planifiees, les femmes rapportant souvent cesser l'alcool apres avoir appris qu'elles etaient enceintes. Cela suggere que l'embryon precoce peut avoir ete hautement expose aux effets nocifs de l'alcool durant la periconception. La fenetre situee entre la periconception et la preimplantation, qui comprend la maturation de l'ovocyte, la fertilisation et la morphogenese de l'embryon avant l'implantation, est une periode particulierement sensible du developpement. A l'interieur de l'oviducte et de l'uterus, l'embryon est expose a un environnement nutritionnel unique qui facilite son developpement et etablit l'expression de novo du genome a travers la reprogrammation epigenetique. L'alcool exerce des effets multiples sur le stress cellulaire et sur les voies de signalisation hormonales et nutritionnelles, qui peuvent affecter le developpement et le metabolisme de cet embryon precoce. Dans cette synthese, les auteurs resument les consequences developpementales indesirables de l'exposition precoce a l'alcool avant l'implantation dans des modeles animaux, et discutent des mecanismes potentiels qui peuvent survenir a l'interieur de l'environnement protege de l'oviducte et de l'uterus. La synthese reduite d'acide retinoique est un mecanisme candidat interessant car il est implique dans le controle de la reprogrammation epigenetique et l'engagement vers un lignage cellulaire particulier, processus qui peuvent avoir des consequences indesirables dans la formation du placenta et, subsequemment, dans la programmation foetale. [Traduit par la Redaction] Mots-cles : ethanol, programmation, embryon, epigenetique, acide retinoique., Introduction It is well established that the period around conception is a 'critical window' during development, in which suboptimal conditions can result in the programming of adult disease (Kwong et [...]

Abstract: To ensure homeostasis, ectothermic organisms adapt to environmental variations through molecular mechanisms. We previously reported that during the seasonal acclimatization of the common carp Cyprinus carpio, molecular and cellular [...]

Eleven specimens of the threatened Loggerhead Sea Turtle (Caretta caretta (L., 1758)) were caught accidentally by fishermen in different parts of Sicily (Mediterranean Sea). Five of them showed an atypical number of carapacial and plastron scutes, making the immediate identification of the specimens as C. caretta difficult. Both genetic and epigenetic analysis were carried out on these specimens. Sequencing of a 649 bp sequence of the mitochondrial cytochrome c oxidase I (COI) gene allowed us to classify all the individuals as C. caretta. Epigenetic analysis, performed by evaluating the total level of DNA cytosine methylation, showed a reduced and significant (F = 72.65, p < 0.01) global level of methylated cytosines in the turtles with nonmodal scutes compared with the normal turtles. Our results suggest that the variability in the number of scutes could be dependent on the environmental conditions during embryonic incubation, via an epigenetic mechanism. This finding could have implications in our understanding of the pathways of morphological evolution and diversification in the chelonians. Key words: Caretta caretta, Loggerhead Sea Turtle, Mediterranean Sea, nonmodal scutes, cytosine methylation, epigenetics. Onze specimens de la tortue caouanne (Caretta caretta (L., 1758)) ont ete captures accidentellement par les pecheurs dans differentes parties de la Sicile (Mediterranee). Cinq d'entre eux ont montre un nombre atypique de plaques de la carapace et plastron, ce qui rend l'identification immediate des specimens C. caretta difficile. Des analyses genetiques et epigenetiques ont ete effectues sur ces echantillons. Le sequencage d'une sequence de 649 pb du cytochrome c oxydase mitochondriale I (COI) a permis de classer tous les individus comme C. caretta. L'analyse epigenetique, realisee en evaluant le niveau total de la methylation du cytosine de l'ADN, a montre un niveau significatif de cytosines methyles (F = 72,65, p < 0,01) dans les individus avec de plaques surnumeraires par rapport aux normales. Nos resultats indiquent que la variabilite du nombre de plaques pourrait dependre des conditions environnementales pendant l'incubation de l'embryon, par l'intermediaire d'un mecanisme epigenetique. Cette decouverte pourrait avoir des implications comprehensives des voies d'evolution morphologique et la diversification chez les cheloniens. Mots-cles: Caretta caretta, tortue caouanne, mer Mediterranee, plaques surnumeraires, methylation de la cytosine, epigenetique., Introduction In the last decade, it was suggested that natural phenotypic variations in response to environmental changes can be generated through a suite of epigenetic mechanisms (Bossdorf et al. 2008). [...]

Abstract: Epidemiologic studies have revealed that diets rich in sulforaphane (SFN), an isothiocyanate present in cruciferous vegetables, are associated with a marked decrease in prostate cancer incidence. The chemo-preventive role [...]

Abstract: Within the past two decades, the fields of chromatin structure and function and transcription regulation research started to fuse and overlap, as evidence mounted to support a very strong [...]

Abstract: The heterochromatin protein 1 (HP1) gene family includes a set of paralogs in higher eukaryotes that serve fundamental roles in heterochromatin structure and maintenance, and other chromatin-related functions. At [...]

Abstract: The sarcoplasmic reticulum (SR) calcium pump (SERCA) and its regulator phospholamban are required for cardiovascular function. Phospholamban alters the apparent calcium affinity of SERCA in a process that is [...]

Genes and environment make the organism. Darwin stood firm in his denial of any direct role of environment in the modification of heredity. His theory of evolution heralded two debates: one about the importance and adequacy of natural selection as the main mechanism of evolution, and the other about the role of genes versus environment in the modification of phenotype and evolution. Here, I provide an overview of the second debate and show that the reasons for the gene versus environment battle were twofold: first, there was confusion about the role of environment in modifying the inheritance of a trait versus the evolution of that trait, and second, there was misunderstanding about the meaning of environment and its interaction with genes in the production of phenotypes. It took nearly a century to see that environment does not directly affect the inheritance of a phenotype (i.e., its heredity), but it is nevertheless the primary mover of phenotypic evolution. Effects of genes and environment are not separate but interdependent. One cannot separate the effect of genes from that of environment, or nature from nurture. To answer the question posed in the title, it is partly because the 20th century has been a century of unending progress in genetics. But also because unlike physics, biology is not colorblind; progress in biology has often been delayed beyond the Kuhnian paradigm change due to built-in interest in negating the influence of environment. Those who are against evolution, of course, cannot be expected to understand the role of environment in evolution. Those for it, many biologists included, believing in the supremacy of genes empowers them by giving adaptation a solely gene-directed (self-driven) 'teleological' interpretation. Key words: gene-environment interaction, norm of reaction, phenotypic plasticity, heritability, canalization, epigenetics, genomics, genetic assimilation. Les genes et l'environnement faconnent l'organisme. Darwin s'est montre inebranlable dans la denegation d'un role direct de l'environnement dans la modification de l'heredite. Sa theorie de l'evolution s'est averee un precurseur de deux debats, l'un sur l'importance et l'adequation de la selection naturelle comme principal mecanisme devolution et l'autre sur le role des genes et de l'environnement dans la modification du phenotype et de l'evolution. Dans ce texte, l'auteur donne un apercu du second debat et montre que les sources du debat genes vs environnement etaient de deux ordres: d'abord, il y eu confusion en ce qui a trait au role de l'environnement dans la modification de l'heredite d'un caractere vs l'evolution de ce caractere ; ensuite, il y a eu un malentendu sur le sens a donner a l'environnement et son interaction avec les genes pour produire des phenotypes. Il a fallu pres d'un siecle pour comprendre que l'environnement n'affecte pas directement l'heredite d'un phenotype, mais qu'il est neanmoins l'agent principal de l'evolution phenotypique. Les effets des genes et de l'environnement ne sont pas distincts mais plutot interdependants. On ne peut separer l'effet des genes de celui de l'environnement, l'inne de l'acquis. Pour repondre a la question posee dans le titre, c'est en partie parce que le vingtieme siecle s'est avere une periode de progres constant en genetique. Mais aussi que, contrairement a la physique, labiologie n'est pas daltonienne ; les progres en biologie ont souvent ete retardes au-dela du changement paradigmatique kuhnien en raison de la volonte inherente de nier l'influence de l'environnement. Bien sur, on ne peut s'attendre a ce que ceux qui sont opposes a l'evolution puissent comprendre le role de l'environnement dans l'evolution. Pour ceux en faveur de l'evolution, incluant plusieurs biologistes, croire en la suprematie des genes renforce leur conviction en conferant a l'adaptation une interpretation <> qui serait uniquement mue par les genes (autonome). [Traduit par la Redaction] Mots-cles : interaction genes-environnement, norme de reaction, plasticite phenotypique, heritabilite, canalisation, epigenetique, genomique, assimilation genetique., Erwin Schrodinger differentiated the unphilosophical and philosophical man as follows: ... the first accepts everything that happens as regards its general form, and finds occasion for surprise only in that [...]

Prostate cancer is a disease that is greatly affected by lifestyle, particularly diet, and is more prevalent in US and European countries compared with South and East Asia. Among several known causes and risk factors, nutrition plays an important role in prostate cancer pathogenesis. Various dietary components including polyphenols have been shown to possess anticancer properties. Dietary polyphenols have been the subject of extensive studies for the last decade because of their anticancer and chemopreventive potentials. Besides possessing various antitumor properties, dietary polyphenols also contribute to epigenetic changes associated with the fate of cancer cells and have emerged as potential drugs for therapeutic intervention. Various polyphenols have been shown to affect DNA methylation, histone posttranslational modifications, and microRNA expression patterns in prostate cancer. In this review, we discuss the contribution of dietary polyphenols to various epigenetic modifications in prostate cancer. Since prostate cancer and diet are intimately associated, polyphenol-rich diets that epigenetically modify tumor biology have great significance in the prevention and management of prostate cancer. Key words: prostate cancer, dietary polyphenols, chemoprevention, epigenetics, DNA methylation, histone modification, microRNA, apoptosis, growth arrest. Le cancer de la prostate est une maladie grandement affectee par le style de vie, particulierement la diete, et il est plus frequent aux Etats-Unis et dans les pays europeens comparativement a l'Asie de sud et de l'est. Parmi les nombreuses causes et facteurs de risques connus, la nutrition joue un role important dans la pathogenese du cancer de la prostate. Plusieurs composants de la diete dont les polyphenols se sont reveles posseder des proprietes anticancereuses. Les polyphenols alimentaires ont ete l'objet d'etudes approfondies au cours de la derniere decennie a cause de leur potentiel anticancereux et chimio-preventif. En plus de posseder differentes proprietes anti-tumorales, les polyphenols alimentaires contribuent aussi aux changements epigenetiques associes a la destinee des cellules cancereuses, et ils sont apparus comme medicaments potentiels en vue d'une intervention therapeutique. On a montre que les polyphenols affectaient la methylation de l'ADN, les modifications post-traductionnelles des histones et les patrons d'expression des micro-ARN dans le cancer de la prostate. Dans cet article de synthese, nous discutons de la contribution des polyphenols alimentaires aux differentes modifications epigenetiques dans le cancer de la prostate. Puisque le cancer de la prostate et la diete sont intimement lies, des dietes riches en polyphenols qui modifient de maniere epigenetique la biologie tumorale sont d'une grande importance dans la prevention et la gestion du cancer de la prostate. [Traduit par la Redaction] Mots-cles: cancer de la prostate, polyphenols alimentaires, chimio-prevention, epigenetique, methylation de l'ADN, modification des histones, micro-ARN, apoptose, arret de la croissance., Introduction Phenolic compounds are found in a large variety of foods such as berries, fruits, legumes, nuts, and vegetables, as well as beverages such as teas, coffees, beers, and wines. [...]

The self-regenerating property of the adult myocardium is not a new discovery. Even though we could not confirm that the adult myocardium is a post-mitotic tissue, we should consider that its plasticity is extremely low. Studies are still in progress to decipher the mechanisms underlying the abovementioned potential fetal features of the adult heart. The modest results of several clinical trials based on the transplantation of millions of autologous stem cells into the dysfunctional heart have confirmed that the cross-talk of different signals, such as the microenvironment, promotes the regeneration of adult myocardium. Recent scientific evidence has revealed that cellular cross-talk does not depend on the action of a single cell phenotype. It is conceivable that the limited turnover of cardiomyocytes is ensured by the interplay of adult cardiac cells in response to environmental changes. The epigenetic state of a cell serves as a dynamic interface between the environment and phenotype. The epigenetic modulation of the adult cardiac cells by natural active compounds encourages further studies to improve myocardial plasticity. In this review, we will highlight the most relevant studies demonstrating the epigenetic modulation of myocardial regeneration without the use of stem cell transplantation. Key words: epigenetic, myocardial regeneration, microenvironment, heart, stem cells. La propriete d'auto-regeneration du myocarde adulte n'est pas une nouvelle decouverte. Bien que nous ne puissions confirmer que le myocarde adulte est un tissu post-mitotique, nous devrions considerer sa plasticite comme extremement faible. Des etudes sont toujours en cours afin de decortiquer les mecanismes qui sous-tendent ces caracteristiques possiblement foetales du coeur adulte. Les resultats modestes de plusieurs essais cliniques bases sur la transplantation de millions de cellules souches autologues dans le coeur dysfonctionnel ont confirme que la communication croisee de differents signaux comme le microenvironnement favorise la regeneration du myocarde adulte. Des donnees scientifiques recentes ont revele que la communication croisee cellulaire ne depend pas de l'action d'un phenotype cellulaire unique. On peut concevoir que le renouvellement limite des cardiomyocytes soit assure par l'interaction de cellules cardiaques adultes en reponse a des changements environnementaux. L'etat epigenetique d'une cellule sert d'interface dynamique entre l'environnement et le phenotype. La modulation epigenetique des cellules cardiaques adultes par des composes naturels actifs nous encourage a realiser davantage d'etudes afin d'ameliorer la plasticite myocardique. Dans cet article de synthese, nous mettrons en evidence les etudes les plus pertinentes qui demontrent une modulation epigenetique de la regeneration myocardique sans utilisation de la transplantation de cellules souches. [Traduit par la Redaction] Mots-cles : epigenetique, regeneration myocardique, microenvironnement, coeur, cellules souches., Introduction Up to 15 years ago, the adult myocardium was not widely considered a self-renewing tissue, even if the rare mitosis of adult cardiomyocytes was already detected in the human [...]

Oxidative stress plays an important role in the development and progression of chronic diabetic complications. Diabetes causes mitochondrial superoxide overproduction in the endothelial cells of both large and small vessels. This increased superoxide production causes the activation of several signal pathways involved in the pathogenesis of chronic complications. In particular, endothelial cells are major targets of glucose-induced oxidative damage in the target organs. Oxidative stress activates cellular signaling pathways and transcription factors in endothelial cells including protein kinase C (PKC), c-Jun-Nterminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), forkhead box O (FOXO), and nuclear factor kappa-B (NF-κB). Oxidative stress also causes DNA damage and activates DNA nucleotide excision repair enzymes including the excision repair cross complimenting 1(ERCC1), ERCC4, and poly(ADP-ribose) polymerase (PARP). Augmented production of histone acetyltransferase p300, and alterations of histone deacetylases, including class III deacetylases sirtuins, are also involved in this process. Recent research has found that small noncoding RNAs, like microRNA, are a new kind of regulator associated with chronic diabetic complications. There are extensive and complicated interactions and among these molecules. The purpose of this review is to demonstrate the role of oxidative stress in the development of diabetic complications in relation to epigenetic changes such as acetylation and microRNA alterations. Key words: oxidative stress, diabetic complications, epigenetics, microRNA, acetylation, p300, SIRT1. Le stress oxydant joue un role important dans le developpement et la progression des complications chroniques du diabete. Le diabete provoque une surproduction de superoxyde mitochondrial dans les cellules endotheliales des grands et des petits vaisseaux. Cette production accrue de superoxyde cause une activation de plusieurs voies de signalisation impliquees dans la pathogenese des complications chroniques. Notamment, les cellules endotheliales sont les cibles principales du dommage oxydatif induit par le glucose dans les organes cibles. Le stress oxydant active des voies de signalisation cellulaires et des facteurs de transcription dans les cellules endotheliales, dont PKC, JNK, MAPK, FOXO et NF-κB. Le stress oxydant produit aussi des dommages a l'ADN et active les enzymes de reparation par excision ERCC1, ERCC4 et la poly(ADP)ribose polymerase (PARP). La production accrue d'histone acetyltransferase p300 et les modifications d'histone deacetylases dont les sirtuines, des deacetylases de classe III, sont aussi impliquees dans ce processus. Des travaux de recherche recents ont montre que les petits ARN non codants comme les microARN constituent une nouvelle classe de regulateurs associes aux complications diabetiques chroniques. Les interactions entre ces molecules sont vastes et complexes. Le but de cet article de synthese est de demontrer le role du stress oxydant dans le developpement des complications diabetiques en relation avec les changements epigenetiques comme l'acetylation et la modification des microARN. [Traduit par la Redaction] Mots-cles: stress oxydant, complications diabetiques, epigenetique, microARN, acetylation, p300, SIRT1., Introduction Diabetes is one of the most common conditions in the world, and diabetic patients may suffer from a wide variety of chronic complications, including retinopathy, cardiomyopathy, and nephropathy. The [...]

Position effect variegation (PEV) refers to quasi-stable patterns of gene expression that are observed at specific loci throughout the genomes of eukaryotes. The genes subjected to PEV can be completely silenced or fully active. Stochastic conversions between these 2 states are responsible for the variegated phenotypes. Positional variegation is used by human pathogens (Trypanosoma, Plasmodium, and Candida) to evade the immune system or adapt to the host environment. In the yeasts Saccharomyces cerevisiae and Saccharomyces pombe, telomeric PEV aids the adaptation to a changing environment. In metazoans, similar epigenetic conversions are likely to accompany cell differentiation and the setting of tissue-specific gene expression programs. Surprisingly, we know very little about the mechanisms of epigenetic conversions. In this article, earlier models on the nature of PEV are revisited and recent advances on the dynamic nature of chromatin are reviewed. The normal dynamic histone turnover during transcription and DNA replication and its perturbation at transcription and replication pause sites are discussed. It is proposed that such perturbations play key roles in epigenetic conversions and in PEV. Key words: Position effect variegation, gene silencing, epigenetic conversions, epigenetics. La variegation par effet de position (VEP) refere a des patrons d'expression genique quasi-stables qui sont observes a des locus specifiques a travers le genome des eucaryotes. Les genes sujets a la VEP peuvent etre tenus completement silencieux ou etre pleinement actifs. Les conversions stochastiques entre ces deux etats sont responsables des phenotypes varieges. La variegation positionnelle est utilisee par les pathogenes humains (Trypanosoma, Plasmodium, Candida) pour s'evader du systeme immunitaire ou s'adapter a l'environnement de l'hote. Chez les levures S. cerevisiae et S. pombe la variegation par effet de position telomerique facilite l'adaptation a un environnement changeant. Chez les metazoaires, des conversions epigenetiques similaires accompagnent probablement la differenciation cellulaire et l'etablissement des programmes d'expression genique specifiques aux tissus. De maniere surprenante, nous connaissons tres peu de choses des mecanismes de conversions epigenetiques. Dans cet article, des modeles anterieurs de la nature de la VEP sont reexmines et les progres recents portant sur la nature dynamique de la chromatine sont passes en revue. La dynamique normale du renouvellement des histones lors de la transcription et la replication de l'ADN, et sa perturbation aux sites de pause de la transcription et de la replication est discutee. Nous proposons que de telles perturbations jouent un role cle dans les conversions epigenetiques et dans la variegation par effet de position. [Traduit par la Redaction] Mots-cles: variegation par effet de position, silencage genque, conversions epigenetiques, epigenetique., Gene silencing and position effect variegation Position effect variegation (PEV) was initially described as a patchy red/white color pattern in the eyes of Drosophila (Muller and Altenburg 1930). This phenotype [...]

Plants undergo changes in response to biotic and abiotic stresses that help them adjust and survive. Some of these changes may even be passed on to progeny and eventually lead to adaptive evolution. Transgenerational changes in response to stress include alterations in DNA methylation and changes in homologous recombination frequency (HRF). The progeny of plants that were stressed often show elevated HRF as well as genomic hypermethylation, although specific loci that are beneficial in times of stress may be hypomethylated. One of the possible mechanisms responsible for passing the memory to the progeny involves small interfering RNAs; Dicer-like proteins, DCL2 and DCL3, are in part required for this process. However, while epigenetic modifications are often present in the untreated progeny of stressed plants, they are not usually sustained for multiple unexposed generations. Still, transgenerational inheritance of such changes has already begun to provide evidence for an important role of epigenetics in enhancing stress resistance. Key words: homologous recombination, DNA methylation, plant stress response, epigenetic regulation, transgenerational effect, adaptive evolution. Les vegetaux subissent des changements en reponse a des stress biotiques et abiotiques qui les aident a s'ajuster et a survivre. Certains de ces changements peuvent meme etre transmis a leur progeniture et conduire eventuellement a une evolution adaptative. Les changements trans-generationnels en reponse au stress incluent les modifications de la methylation d'ADN et les changements de frequence de recombinaison homologue (FRH). La progeniture de vegetaux qui ont ete stresses presente souvent des niveaux eleves de FRH de meme qu'une hypermethylation genomique, meme si les locus specifiques benefiques en situation de stress peuvent etre hypomethyles. Un des possibles mecanismes responsables du transfert de memoire a la progeniture implique les petits ARN interferents, les proteines de type DICER DCL2 et DCL3, qui sont en partie necessaire a ce processus. Cependant, alors que les modifications epigenetiques sont souvent presentes chez la progeniture non traitee de vegetaux stresses, elles ne sont habituellement pas durables pendant de multiples generations non exposees. Quoi qu'il en soit, l'heritabilite trans-generationnelle de tels changements a deja commence a fournir une preuve du role important de l'epigenetique dans l'augmentation de la resistance au stress. [Traduit par la Redaction] Mots-cles : recombinaison homologue, methylation d'ADN, reponse au stress chez les vegetaux, regulation epigenetique, effet trans-generationnel, evolution adaptative., Introduction Plants are an extremely important source of nutrition for our growing global population, and agriculture plays a key role in the economy of many countries. Because of their stationary [...]

The impact of diet and environmental factors on genes concerned with epigenetic inheritance and the mechanism of evolution has grown significantly beyond the Modern Synthesis period. Epigenetic inheritance is the passing of phenotypic change to subsequent generations in ways that are outside the genetic code of DNA. Recently, polymorphisms of the human Delta-5 (fatty acid desaturase, FADS1) and Delta-6 (FADS2) desaturase genes have been described as being associated with the level of several long-chain n-3 and n-6 polyunsaturated fatty acids (PUFAs) in serum phospholipids. Increased consumption of refined starches and sugar increases the generation of superoxide anion in the tissues and free fatty acids (FFA) in the blood. There is an increased amount and activity of nuclear factor-[kappa]B (NF-[kappa]B), a transcriptional factor regulating the activity of at least 125 genes, most of which are pro-inflammatory. The consumption of glucose may be associated with an increase in 2 other pro-inflammatory transcription factors: activating protein-1 (AP-1), and early growth response protein-1 (Egr-1). AP-1 regulates the transcription of matrix metallo-proteinases and Egr-1 modulates the transcription of tissue factor and plasminogen activator inhibitor-1. It is possible that a complex set of factors, including nutritional factors, come into play during epigenetic inheritance. Key words: epigenetic inheritance, TsimTsoum concept, evolution, diet. L'impact de la diete et des facteurs environnementaux sur les genes concernant l'heredite epigenetique et les mecanismes d'evolution, depasse ce qui avait ete envisage dans Modern Synthesis.L'heredite epigenetique definit la transmission d'un changement phenotypique a des generations subsequentes de maniere externe au code genetique d'ADN. Recemment, les polymorphismes des genes codant les desaturases Delta-5 (desaturase d'acide gras, FADS1) et Delta-6 (FADS2) ont ete decrits pour etre associes au niveau de plusieurs acides gras polyinsatures a longue chaine n-3 et n-6 dans les phospholipides seriques. L augmentation de la consommation de farines et de sucres raffines augmente la generation d anion superoxyde dans les tissus et des acides gras libres dans le sang. Il s en suit une augmentation de la quantite et de l'activite du facteur NF-[kappa]B, un facteur de transcription qui regule l'activite d'au moins 125 genes dont la majorite est proinflammatoire. La consommation de glucose peut etre associee a une augmentation de deux autres facteurs de transcription pro-inflammatoires : AP-1 (activating protein-1) et Egr-1 (early growth response protein-1). AP-1 regule la transcription des metalloproteases de la matrice et Egr-1 module la transcription du facteur tissulaire TF et de l'inhibiteur de l'activateur du plasminogene PAI-1. Il est possible qu un jeu complexe de facteurs, incluant des facteurs nutritionnels, soit mis en jeu lors de l heredite epigenetique. Mots-cles : heredite epigenetique, concept TsimTsoum, evolution, diete. [Traduit par la Redaction], Introduction There is evidence that primary risk factors such as diet, physical inactivity, tobacco, stress, pollutants, radiation, and drugs can influence genetic structure and function. There has been much discussion [...]

Meiotic metaphase I configuration frequencies were determined in different tillers of genetically related plants of rye (Secale cereale L.) heterozygous for reciprocal translocation T248W (between chromosome arms 1RS and 6RS) and with an additional (telocentric) arm 1RS. Seventeen different configurations could be recognized, grouped into three categories. Very different configuration frequencies were found not only between sister plants from the same parents but also between tillers of the same plant grown under identical conditions (climate chambers at 15°C and 20°C). The heterogeneity reflects variation in chromosome pairing and crossing over, and is variable and unpredictable. Anthers within florets were homogeneous. Between tiller heterogeneity is insufficient to explain differences between sister plants. It is ascribed to random somatic variation in the conditions of the chromatin which, at meiosis, govern chromosome pairing. During sexual differentiation, these conditions are fixed and subsequent cell lineages have the same pairing and crossing over characteristics. As homology search is an activity of DNA, this control of pairing and crossing over, consistent over long cell lineages, may be considered to be epigenetic even when no realistic suggestions concerning its character can be given. Key words: translocation heterozygote, single-arm-trisomiy, Secale, meiosis, intraplant heterogeneity. Les frequences des configurations observees lors de la metaphase I de la meiose ont ete mesurees au sein de differents talles de chacun de plusieurs plants de seigle (Secale cereale L.) genetiquement apparentes et heterozygotes pour la translocation reciproque T248W (entre bras chromosomiques 1RS et 5RS) ainsi que porteurs d'un bras (telocentrique) 1RS additionnel. Dix-sept configurations differentes ont ete distinguees et formaient trois categories. Des frequences tres differentes de ces configurations ont ete observees non seulement entre plantes soeurs ayant les memes parents, mais aussi entre talles de la meme plante cultivee dans des conditions identiques (chambres de croissance a 15°C ou 20°C). Cette heterogeneite reflete de la variation au niveau de l' appariement chromosomique et des enjambements, est variable et imprevisible. Les antheres au sein d' une fleur etaient homogenes. L' heterogeneite observee entre talles etait insuffisante pour expliquer les differences entre plantes soeurs. Ces dernieres sont plutot attribuees a une variation somatique aleatoire dans l' etat de la chromatine qui, lors de la meiose, determinerait l' appariement. Au cours de la differenciation sexuelle, ces conditions seraient fixees et les lignees cellulaires derivees partageraient les memes caracteristiques en matiere d'appariement et de recombinaison. Comme la recherche d'homologie est un processus qui depend de l'ADN, on peut considerer ce controle de l' appariement et de l' enjambent, conserve tout au long de lignees cellulaires, comme etant un processus epigenetique bien qu'aucune hypothese realiste concernant sa nature ne puisse etre mise de l'avant. Mots-cles : heterozygote pour une translocation, trisomie pour un seul bras, Secale, meiose, heterogeneite intra- plante. [Traduit par la Redaction], Introduction Detailed reports on variation in meiotic behaviour within individual organisms are rare. Sybenga et al. (2008) reported on the variation between tillers of single plants of rye (Secale cereale [...]

This review addresses the mechanisms by which epigenetic variation modulates plant gene regulation and phenotype. In particular we explore the scope for harnessing such processes within the context of crop genetic improvement. We focus on the role of DNA methylation as an epigenetic mark that contributes to epiallelic diversity and modulation of gene regulation. We outline the prevalence and distribution of epigenetic marks in relation to eukaryote developmental processes, and in particular identify where this may be relevant to crop traits both in terms of specific developmental stages and in relation to physiological responses to environmental change. Recent whole genome surveys have identified specific characteristics of the distribution of DNA methylation within plant genomes. Together with greater understanding of the mode of action of different maintenance and de novo methyltransferases, this provides an opportunity to modulate DNA methylation status at specific loci as an intervention strategy in crop genetic improvement. We discuss alternative approaches that may be suitable for harnessing such induced epiallelic variation. Most of the discussion is associated with Brassica crops, which demonstrate considerable morphological plasticity, segmental chromosomal duplication, and polyploidy. Key words: epigenetics, crop plants, DNA methylation, breeding, Brassica. Cette synthase porte sur les mecanismes via lesquels la variation eepigeenetique module la regulation genique et le phenotype. En particulier, les auteurs explorent le potentiel d'exploitation de ces processus dans le contexte de l'amelioration genetique. Les auteurs portent leur attention sur la methylation en tant que marqueur epigenetique qui contribue a la diversite epi-allelique et a la modulation de l'expression genique. Les auteurs decrivent la frequence et la distribution des marques epigeenetiques en relation avec les processus du deeveloppement chez les eucaryotes et, en particulier, identifient pourquoi cela pourrait s'averer pertinent chez les especes cultivees tant a des stades precis du deeveloppement qu'en relation avec les reponses physiologiques aux changements environnementaux. Des etudes recentes a l'eechelle du genome entier ont permis d'identifier des caracteristiques specifiques de la distribution des sites de methylation de l'ADN au sein des genomes des plantes. Combine; avec une meilleure comprehension du mode d'action des diverses methyltransfeerases responsables soit de la methylation initiale ou de son maintien, cela offre une opportunite de moduler la methylation a des locus specifiques pour des fins d'amelioration genetique. Les auteurs discutent d'approches alternatives qui pourraient permettre de tirer profit d'une telle variation epi-allelique induite. La plus grande partie de la discussion porte sur les Brassica cultivees, lesquelles presentent une plasticite morphologique considerable, de la duplication de segments chromosomiques et la polyploidie. Mots-cles: epigenetique, plantes cultivees, methylation de l'ADN, amelioration genetique, Brassica. [Traduit par la Redaction], Introduction Over the past century genetic improvement of crops has underpinned massive increases in yield and food production. This has been achieved primarily through concerted breeding programs based upon crossing [...]

Remodeling and myocardial matrix metabolism contributes to cardiac endothelium-myocyte (perivascular fibrosis), myocyte-myocyte (interstitial fibrosis), and mitochondrion-myocyte (fusion and fission) coupling. Matrix metalloproteinases (MMPs), and tissue inhibitor of metalloproteinases (TIMPs) play differential roles in different tissues and diseases. For example, although present in the heart, MMP-3 is known as stromelysin (i.e., stromal tissue enzyme). Interestingly, TIMP-3 causes apoptosis. Exercise and nutrition are synergistic in the mitigation of diseases: exercise releases exosomes containing miRNAs. Nutrition/vitamins B6 and B12 regulate the metabolism of homocysteine (an epigenetic byproduct of DNA/RNA/protein methylation). Thus, epigenetic silencing is an important therapeutic target. The statistical analysis of cohorts may be less indicative for the treatment of a disease, particularly if the 2 twins are different in terms of responding to the medicine for the same disease, therefore, personalized medicine is the future of therapy. Key words: matrix, endothelium-myocyte coupling, epigenetics, personalized medicine. Le remodelage de la matrice myocardique et son metabolisme contribuent au couplage des cellules endotheliales cardiaques et des myocytes (fibrose perivasculaire), des myocytes entre eux (fibrose interstitielle) et a la fusion et la fission des mitochondries des myocytes. Les metalloproteases de la matrice (MMP) et l'inhibiteur tissulaire des metalloproteases (TIMP) exercent des roles differentiels en fonction des differents tissus et maladies ; ainsi, meme si elle est presente dans le coeur, la MMP-3 est aussi connue sous le nom de stromelysine (i.e., enzyme du stroma). Fait interessant, TIMP-3 provoque l'apoptose. L'exercice et la nutrition agissent en synergie dans l'attenuation de la maladie ; l'exercice libere des exosomes qui contiennent des pARNi. La nutrition et les vitamines B6 et B12 regulent le metabolisme de l'homocysteine (un sous-produit epigenetique de la methylation de l'ADN, de l'ARN et des proteines). Consequemment, le silencage epigenetique constitue une cible therapeutique importante. Les analyses statistiques de cohortes de patients peuvent etre moins indicatives d'un traitement pour une maladie, particulierement si des jumeaux sont differents en termes de reponses aux medicaments pour la meme maladie; ainsi, la medecine personnalisee est la voie de l'avenir. [Traduit par la Redaction] Mots-cles : matrice, couplage des myocytes endotheliaux, epigenetique, medecine personnalisee., Myocardial matrix metabolism Remodeling, by its very nature, implies synthesis and degradation of the extracellular matrix (ECM) (Tyagi 1997). Matrix metalloproteinases (MMPs) were first discovered in tadpole tail development, revealing [...]

Protein folding for export through the exocytic pathway of the eukaryotic cell is sensitive to the local composition of membrane trafficking components, and requires the assistance of multiple chaperones that define the folding buffer of the cell--the chaperome. Different cell types exploit the variable composition of the chaperome to maintain protein folding homeostasis or proteostasis--an adaptive, celltypespecific biological environment that works through the kinetic and thermodynamic properties of the protein fold to achieve functionality. Proteostasis is now recognized to be linked to the epigenome through histone deacetylase (HDAC)-mediated pathways. Perturbation of these relationships occurs in misfolding diseases, such as cystic fibrosis (CF), where a Phe508 deletion in the NBD1 domain of the multimembrane spanning chloride channel CF transmembrane conductance regulator prevents its delivery to the cell surface. It is now apparent that protein misfolding in disease and in aging can be altered by the use of pharmacological chaperones to stabilize the fold, and (or) by the manipulation of pathways that favor metabolic stability through the use of system specific proteostasis regulators. Newly identified mechanisms that efficiently correct CF suggest a multitarget solution to restore transport and channel function at the cell surface through epigenetic mechanism(s). These results suggest the existence of a tunable range of epigenetic and proteostatic environments that may be used to manage correction of misfolding disease phenotypes., doi: 10.1139/O09-905 W. Balch, D. Hutt, D. Herman, A. Koulov, P. Lapointe, J. Coppinger, S. Pankow, B. Lu, A. Rodriquez, S. Noel, J. Kelly, M. Gentzsch, J. Riordan, E. Sorscher, [...]