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DNA 甲基转移酶抑制剂调节组蛋白甲基化:精子分化过程中 H3K4me3 和 DNA 甲基化之间的表观遗传串扰。

DNA methyltransferase inhibitors modulate histone methylation: epigenetic crosstalk between H3K4me3 and DNA methylation during sperm differentiation.

机构信息

Genetics Department, University of Bucharest, Faculty of Biology, Romania.

'Lucian Blaga' University, Faculty of Medicine, Sibiu, Romania.

出版信息

Zygote. 2021 Jun;29(3):239-244. doi: 10.1017/S0967199420000684. Epub 2021 Jan 8.

DOI:10.1017/S0967199420000684
PMID:33413709
Abstract

The process of cytodifferentiation in spermatogenesis is governed by a unique genetic and molecular programme. In this context, accurate 'tuning' of the regulatory mechanisms involved in germ cells differentiation is required, as any error could have dramatic consequences on species survival and maintenance. To study the processes that govern the spatial-temporal expression of genes, as well as analyse transmission of epigenetic information to descendants, an integrated approach of genetics, biochemistry and cytology data is necessary. As information in the literature on interplay between DNA methylation and histone H3 lysine 4 trimethylation (H3K4me3) in the advanced stages of murine spermatogenesis is still scarce, we investigated the effect of a DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine, at the cytological level using immunocytochemistry methodology. Our results revealed a particular distribution of H3K4me3 during sperm cell differentiation and highlighted an important role for regulation of DNA methylation in controlling histone methylation and chromatin remodelling during spermatogenesis.

摘要

精子发生中的细胞分化过程受独特的遗传和分子程序控制。在这种情况下,需要对涉及生殖细胞分化的调节机制进行精确“调谐”,因为任何错误都可能对物种的生存和维持产生巨大影响。为了研究调控基因时空表达的过程,以及分析表观遗传信息向后代的传递,需要综合运用遗传学、生物化学和细胞学数据。由于文献中关于 DNA 甲基化和组蛋白 H3 赖氨酸 4 三甲基化(H3K4me3)在小鼠精子发生后期相互作用的信息仍然很少,我们使用免疫细胞化学方法在细胞学水平上研究了 DNA 甲基转移酶抑制剂 5-氮杂-2'-脱氧胞苷的作用。我们的结果揭示了 H3K4me3 在精子细胞分化过程中的特定分布,并强调了 DNA 甲基化调控在控制精子发生过程中组蛋白甲基化和染色质重塑中的重要作用。

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