Unité de Formation et de Recherches (UFR) des sciences, Université de Caen Normandie, 14032 Caen CEDEX, France.
Biologie des Organismes et Ecosystèmes Aquatiques (BOREA), FRE2030, Muséum National d'Histoire Naturelle (MNHN), Centre National de la Recherche Scientifique (CNRS), Institut de Recherche et Développement (IRD), Sorbonne Université (SU), Université de Caen Normandie (UCN), Université des Antilles (UA), 75231 Paris CEDEX, France.
Genes (Basel). 2019 Sep 10;10(9):695. doi: 10.3390/genes10090695.
Histone methylation patterns are important epigenetic regulators of mammalian development, notably through stem cell identity maintenance by chromatin remodeling and transcriptional control of pluripotency genes. But, the implications of histone marks are poorly understood in distant groups outside vertebrates and ecdysozoan models. However, the development of the Pacific oyster is under the strong epigenetic influence of DNA methylation, and histone-demethylase orthologues are highly expressed during . early life. This suggests a physiological relevance of histone methylation regulation in oyster development, raising the question of functional conservation of this epigenetic pathway in lophotrochozoan. Quantification of histone methylation using fluorescent ELISAs during oyster early life indicated significant variations in monomethyl histone H3 lysine 4 (H3K4me), an overall decrease in H3K9 mono- and tri-methylations, and in H3K36 methylations, respectively, whereas no significant modification could be detected in H3K27 methylation. Early in vivo treatment with the JmjC-specific inhibitor Methylstat induced hypermethylation of all the examined histone H3 lysines and developmental alterations as revealed by scanning electronic microscopy. Using microarrays, we identified 376 genes that were differentially expressed under methylstat treatment, which expression patterns could discriminate between samples as indicated by principal component analysis. Furthermore, Gene Ontology revealed that these genes were related to processes potentially important for embryonic stages such as binding, cell differentiation and development. These results suggest an important physiological significance of histone methylation in the oyster embryonic and larval life, providing, to our knowledge, the first insights into epigenetic regulation by histone methylation in lophotrochozoan development.
组蛋白甲基化模式是哺乳动物发育的重要表观遗传调控因子,特别是通过染色质重塑和多能性基因的转录控制来维持干细胞特性。但是,在脊椎动物和节肢动物模型以外的远缘群中,组蛋白标记的意义还知之甚少。然而,太平洋牡蛎的发育受到 DNA 甲基化的强烈表观遗传影响,并且 组蛋白去甲基酶同源物在 早期生命中高度表达。这表明组蛋白甲基化调控在牡蛎发育中具有生理相关性,提出了这种表观遗传途径在 担轮动物中功能保守的问题。使用荧光 ELISA 在牡蛎早期生命中定量组蛋白甲基化表明,组蛋白 H3 赖氨酸 4 的单甲基化(H3K4me)存在显著变化,H3K9 的单甲基化和三甲基化以及 H3K36 的甲基化总体减少,而 H3K27 的甲基化则没有明显修饰。早期体内用 JmjC 特异性抑制剂 Methylstat 处理会诱导所有检测到的组蛋白 H3 赖氨酸发生超甲基化,并通过扫描电子显微镜揭示发育异常。使用微阵列,我们鉴定了 376 个在甲基stat 处理下差异表达的基因,主成分分析表明这些基因的表达模式可以区分样本。此外,基因本体论表明,这些基因与胚胎阶段可能重要的过程有关,如结合、细胞分化和发育。这些结果表明组蛋白甲基化在牡蛎胚胎和幼虫生命中具有重要的生理意义,为我们提供了担轮动物发育中组蛋白甲基化表观遗传调控的第一个见解。