H4K16ac激活了可转移元素的转录,并有助于它们的Cis调节功能
Debosree Pal1, Manthan Patel1, Fanny Boulet1
1Blizard Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK.
Nature structural & molecular biology
|June 12, 2023
概括
基因组H4K16乙化标记了可转移元素 (TE),在发育和癌症期间激活基因转录. 这些表观遗传标记揭示了TEs.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 基因组学就是基因组学.
- 分子生物学分子生物学
背景情况:
- 哺乳动物基因组含有众多可转移元素 (TE),这些元素通常被表观遗传机制沉默.
- 已知TEs在早期发育,神经元分化和各种癌症等特定的生物过程中受到上调.
- 控制TE转录的精确表观遗传因素,特别是在这些上调状态期间,仍然不完全理解.
研究的目的:
- 研究由男性特异性致死性 (MSL) 复合体介导的素H4在素16 (H4K16ac) 的乙化对调节可转移元素转录的作用.
- 确定H4K16ac在TEs中的丰富是否有助于它们在人类胚胎干细胞 (hESC) 和癌细胞中的转录激活和功能作用.
主要方法:
- 在hESC和癌细胞中对TEs进行H4K16ac丰富的分析.
- 评估TE的转录活性,特别是长间隔的核元素 (LINE1s,L1s) 和内源性逆转录病毒长终端重复 (ERVs LTRs).
- 使用染色体特征分析,拓学域边界映射和基因循环相互作用,研究H4K16ac标记的TE的增强器类功能.
- 采用基于CRISPR的表观遗传扰动和L1s的遗传删除来评估cis调节作用.
主要成果:
- 在hESC和癌细胞中的TEs中,H4K16ac被丰富,与特定的全长LINE1s和ERV LTRs的激活相关.
- H4K16ac标记的L1s和LTRs表现出增强器类特征,位于活跃的增强器区域,通常位于拓学相关的域边界.
- 这些TEs与附近的基因进行循环相互作用.
- 表观遗传和遗传乱表明,H4K16ac标记的L1s和LTRs调节了cis.邻近基因的表达.
结论:
- H4K16ac是一种关键的表观遗传标记,促进了特定TE的转录,包括LINE1s和ERV LTRs.
- 这些TEs通过在特定的基因组位点建立和维持活跃的染色质状态,为cis-regulatory景观做出贡献.
- 这些发现突出了MSL复合体介导的H4K16ac在TE调节和发育和疾病期间的基因表达中的新型作用.
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