Sperm histone H3 lysine 4 trimethylation is altered in a genetic mouse model of transgenerational epigenetic inheritance.
Sperm histone H3 lysine 4 trimethylation is altered in a genetic mouse model of transgenerational epigenetic inheritance.
复制标题
DOI：
10.1093/nar/gkaa712
复制
发表时间：
2020-11-18
影响因子：
14.9
通讯作者：
Kimmins S
中科院分区：
文献类型：
--
作者：
Lismer A;Siklenka K;Lafleur C;Dumeaux V;Kimmins S
鉴于过去40年来精子数量减半，以及不能仅用遗传学解释的复杂疾病的增加，推进有关生育和遗传的分子知识变得至关重要。这两种趋势之间的联系可能在于精子表观基因组的改变，并通过环境暴露发生。精子表观基因组的变化也与几代人的健康风险有关，如代谢紊乱和癌症。因此，必须确定在精子发生和胚胎发生过程中逃避重编程的表观遗传修饰。在这里，我们的目的是确定在我们的表观遗传小鼠模型中跨代表型所涉及的染色质标记，该遗传小鼠模型在其生殖细胞中过表达组蛋白去甲基化酶KDM 1A。我们使用精子特异性染色质免疫沉淀，然后进行深度测序（ChIP-seq）和计算分析，以确定组蛋白H3赖氨酸4三甲基化（H3 K4 me 3）和组蛋白H3赖氨酸27三甲基化（H3 K27 me 3）的差异富集是否是通过父系种系进行跨代表观遗传遗传的机制。我们对KDM 1A转基因雄性精子的分析揭示了H3 K4 me 3富集的特定变化，其主要独立于二价H3 K4 me 3/H3 K27 me 3区域发生。在植入前胚胎的父系等位基因上鉴定了精子中具有改变的H3 K4 me 3富集的许多区域。这些结果表明，精子H3 K4 me 3的功能在非遗传表型的传递transgenerally。
Advancing the molecular knowledge surrounding fertility and inheritance has become critical given the halving of sperm counts in the last 40 years, and the rise in complex disease which cannot be explained by genetics alone. The connection between both these trends may lie in alterations to the sperm epigenome and occur through environmental exposures. Changes to the sperm epigenome are also associated with health risks across generations such as metabolic disorders and cancer. Thus, it is imperative to identify the epigenetic modifications that escape reprogramming during spermatogenesis and embryogenesis. Here, we aimed to identify the chromatin signature(s) involved in transgenerational phenotypes in our genetic mouse model of epigenetic inheritance that overexpresses the histone demethylase KDM1A in their germ cells. We used sperm-specific chromatin immunoprecipitation followed by in depth sequencing (ChIP-seq), and computational analysis to identify whether differential enrichment of histone H3 lysine 4 trimethylation (H3K4me3), and histone H3 lysine 27 trimethylation (H3K27me3) serve as mechanisms for transgenerational epigenetic inheritance through the paternal germline. Our analysis on the sperm of KDM1A transgenic males revealed specific changes in H3K4me3 enrichment that predominantly occurred independently from bivalent H3K4me3/H3K27me3 regions. Many regions with altered H3K4me3 enrichment in sperm were identified on the paternal allele of the pre-implantation embryo. These findings suggest that sperm H3K4me3 functions in the transmission of non-genetic phenotypes transgenerationally.
登录
查看更多内容
影响因子：
16.8
作者：
Brykczynska, Urszula;Hisano, Mizue;Peters, Antoine H. F. M.
通讯作者：
Peters, Antoine H. F. M.
影响因子：
5.8
作者：
Ballman, KV;Grill, DE;Therneau, TM
通讯作者：
Therneau, TM
影响因子：
6.7
作者：
Aston, Kenneth I.;Uren, Philip J.;Carrell, Douglas T.
通讯作者：
Carrell, Douglas T.
5-羟甲基胞嘧啶在小鼠精子发生过程中的动态
影响因子：
16.6
作者：
Gan, Haiyun;Wen, Lu;Tang, Fuchou
通讯作者：
Tang, Fuchou
影响因子：
7.7
作者：
Aoshima, Keisuke;Inoue, Erina;Okada, Yuki
通讯作者：
Okada, Yuki