Epigenetic Transgenerational Inheritance of Altered Sperm Histone Retention Sites.

Epigenetic Transgenerational Inheritance of Altered Sperm Histone Retention Sites.
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DOI:
10.1038/s41598-018-23612-y
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发表时间:
2018-03-28
期刊:
影响因子:
4.6
通讯作者:
Skinner MK
Skinner MK
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Ben Maamar M;Sadler-Riggleman I;Beck D;Skinner MK

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各种环境毒物和因素已被证明可诱导疾病的表观遗传和表型变异的跨代遗传。生殖系(精子或卵子)的表观遗传改变是传递跨代表型所必需的。本研究旨在探讨组蛋白在精子中的潜在作用,以帮助介导表观遗传跨代遗传。农业杀菌剂vinclozolin和农药DDT(二氯二苯三氯乙烷)被单独用于促进疾病的表观遗传跨代遗传。从跨代F3代对照和暴露谱系雄性大鼠中收集纯化的附睾尾部精子进行组蛋白分析。使用H3染色质免疫沉淀(ChIP-Seq)分析,在对照系精子中观察到组蛋白H3保留位点的可重复核心。有趣的是,在F3代暴露谱系精子中观察到相同的H3保留位点核心组和额外的差异组蛋白保留位点(DHRs)。虽然观察到新的组蛋白H3保留位点,但在对照组和暴露谱系之间观察到组蛋白修饰(H3K27me3甲基化)的变化可以忽略不计。观察结果表明,除了先前发现的精子DNA甲基化和ncRNA的改变外,差异组蛋白保留位点(DHRs)的诱导似乎也参与了环境诱导的表观遗传跨代遗传。
A variety of environmental toxicants and factors have been shown to induce the epigenetic transgenerational inheritance of disease and phenotypic variation. Epigenetic alterations in the germline (sperm or egg) are required to transmit transgenerational phenotypes. The current study was designed to investigate the potential role of histones in sperm to help mediate the epigenetic transgenerational inheritance. The agricultural fungicide vinclozolin and the pesticide DDT (dichlorodiphenyltrichloroethane) were independently used to promote the epigenetic transgenerational inheritance of disease. Purified cauda epididymal sperm were collected from the transgenerational F3 generation control and exposure lineage male rats for histone analysis. A reproducible core of histone H3 retention sites was observed using an H3 chromatin immunoprecipitation (ChIP-Seq) analysis in control lineage sperm. Interestingly, the same core group of H3 retention sites plus additional differential histone retention sites (DHRs) were observed in the F3 generation exposure lineage sperm. Although new histone H3 retention sites were observed, negligible change in histone modification (methylation of H3K27me3) was observed between the control and exposure lineages. Observations demonstrate that in addition to alterations in sperm DNA methylation and ncRNA previously identified, the induction of differential histone retention sites (DHRs) also appear to be involved in environmentally induced epigenetic transgenerational inheritance.
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