The complex pattern of epigenomic variation between natural yeast strains at single-nucleosome resolution

International audienceBackground: Epigenomic studies on humans and model species have revealed substantial inter‑individual variation in histone modification profiles. However, the pattern of this variation has not been precisely characterized, particularly regarding which genomic features are enriched for variability and whether distinct histone marks co‑vary synergistically. Yeast allows us to investigate intra‑species variation at high resolution while avoiding other sources of variation, such as cell type or subtype. Results: We profiled histone marks H3K4me3, H3K9ac, H3K14ac, H4K12ac and H3K4me1 in three unrelated wild strains of Saccharomyces cerevisiae at single‑nucleosome resolution and analyzed inter‑strain differences statistically. All five marks varied significantly at specific loci, but to different extents. The number of nucleosomes varying for a given mark between two strains ranged from 20 to several thousands; +1 nucleosomes were significantly less subject to variation. Genes with highly evolvable or responsive expression showed higher variability; however, the variation pattern could not be explained by known transcriptional differences between the strains. Synergistic variation of distinct marks was not systematic, with surprising differences between functionally related H3K9ac and H3K14ac. Interestingly, H3K14ac differences that persisted through transient hyperacetylation were supported by H3K4me3 differences, suggesting stabilization via cross talk. Conclusions: Quantitative variation of histone marks among S. cerevisiae strains is abundant and complex. Its relation to functional characteristics is modular and seems modest, with partial association with gene expression divergences, differences between functionally related marks and partial co‑variation between marks that may confer stability. Thus, the specific context of studies, such as which precise marks, individuals and genomic loci are investigated, is primor‑ dial in population epigenomics studies. The complexity found in this pilot survey in yeast suggests that high complexity can be anticipated among higher eukaryotes, including humans

Étude des modifications de l'hémostase et des multimères de facteur von Willebrand en peropératoire et postopératoire précoce de la mise en place d'une assistance circulatoire mécanique : thèse présentée pour le diplôme de docteur en médecine, diplôme d'É

Médecine (anesthésie-réanimation)L’utilisation de dispositifs d’assistance circulatoire mécanique (ACM) est une alternative récente à la transplantation cardiaque en cas d’insuffisance cardiaque terminale. L’objectif de notre étude est de décrire les modifications de l’hémostase, et en particulier du facteur von Willebrand (FvW), au cours des périodes per et postopératoires précoces de la mise en place d’une ACM. En cas d’implantation d’une ACM, il existe une dégradation précoce, dès la 6ème heure suivant le démarrage, des multimères de FvW (p-0.01). Ces anomalies pourraient contribuer de manière significative aux troubles de l’hémostase observés dans la période postopératoire immédiate. Une correction de ces anomalies pourrait s’avérer utile en cas de saignement postopératoire précoc

Place du pharmacien d'officine dans la prise en charge du patient cancéreux (enquête en Bourgogne)

DIJON-BU Médecine Pharmacie (212312103) / SudocSudocFranceF

Natural sequence variants of yeast environmental sensors confer cell-to-cell expression variability.

: Living systems may have evolved probabilistic bet hedging strategies that generate cell-to-cell phenotypic diversity in anticipation of environmental catastrophes, as opposed to adaptation via a deterministic response to environmental changes. Evolution of bet hedging assumes that genotypes segregating in natural populations modulate the level of intraclonal diversity, which so far has largely remained hypothetical. Using a fluorescent Pmet17-GFP reporter, we mapped four genetic loci conferring to a wild yeast strain an elevated cell-to-cell variability in the expression of MET17, a gene regulated by the methionine pathway. A frameshift mutation in the Erc1p transmembrane transporter, probably resulting from a release of laboratory strains from negative selection, reduced Pmet17-GFP expression variability. At a second locus, cis-regulatory polymorphisms increased mean expression of the Mup1p methionine permease, causing increased expression variability in trans. These results demonstrate that an expression quantitative trait locus (eQTL) can simultaneously have a deterministic effect in cis and a probabilistic effect in trans. Our observations indicate that the evolution of transmembrane transporter genes can tune intraclonal variation and may therefore be implicated in both reactive and anticipatory strategies of adaptation

Inflammation, Oxidative Stress, Senescence in Atherosclerosis: Thioredoxine-1 as an Emerging Therapeutic Target

International audienceAtherosclerosis is a leading cause of cardiovascular diseases (CVD) worldwide and intimately linked to aging. This pathology is characterized by chronic inflammation, oxidative stress, gradual accumulation of low-density lipoproteins (LDL) particles and fibrous elements in focal areas of large and medium arteries. These fibrofatty lesions in the artery wall become progressively unstable and thrombogenic leading to heart attack, stroke or other severe heart ischemic syndromes. Elevated blood levels of LDL are major triggering events for atherosclerosis. A cascade of molecular and cellular events results in the atherosclerotic plaque formation, evolution, and rupture. Moreover, the senescence of multiple cell types present in the vasculature were reported to contribute to atherosclerotic plaque progression and destabilization. Classical therapeutic interventions consist of lipid-lowering drugs, anti-inflammatory and life style dispositions. Moreover, targeting oxidative stress by developing innovative antioxidant agents or boosting antioxidant systems is also a well-established strategy. Accumulation of senescent cells (SC) is also another important feature of atherosclerosis and was detected in various models. Hence, targeting SCs appears as an emerging therapeutic option, since senolytic agents favorably disturb atherosclerotic plaques. In this review, we propose a survey of the impact of inflammation, oxidative stress, and senescence in atherosclerosis; and the emerging therapeutic options, including thioredoxin-based approaches such as anti-oxidant, anti-inflammatory, and anti-atherogenic strategy with promising potential of senomodulation