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系统评估逆转录病毒LTRs作为小鼠胚胎中的cis-regulatory元素

Jian Yang¹, Lauryn Cook¹, Zhiyuan Chen¹

¹Reproductive Sciences Center, Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.

|February 21, 2024

概括

哺乳动物的逆转移体,如MT2_Mm,在早期发育过程中被重新激活. 使用CRISPR干扰来破坏这些元素,揭示了它们在基因调节和胚胎进展中的关键作用.

科学领域:

发展生物学发展生物学
基因组学就是基因组学.
表观遗传学在表观遗传学中,表观遗传学是指表观遗传学.

背景情况:

逆转移体,特别是长终端重复 (LTR) 元素,在哺乳动物细胞基因组激活 (ZGA) 过程中被重新激活.
了解早期发育中的众多逆转移子插入的功能是具有挑战性的.
MT2_Mm是已知的ZGA和全能性标记物,在小鼠中进行了数千次基因组插入.

研究的目的:

在哺乳动物早期发育过程中调查MT2逆转移素激活的功能重要性.
系统地定义小鼠胚胎中MT2元素的 cis调节功能.
为了克服同时操纵数千个逆转移子插入的挑战.

主要方法:

使用CRISPR干扰 (CRISPRi) 来扰乱2细胞小鼠胚胎中的MT2_Mm和MT2C_Mm长终端重复插入 (LTR).
功能性扰动与多原子分析相结合.
在整个基因组中评估了染色质可访问性和基因组修饰 (H3K27ac).

主要成果:

克里斯皮尔成功扰乱了超过93%的MT2_Mm和55%的MT2C_Mm插入.
这种干扰导致了数百个囊基因组激活 (ZGA) 基因的下调.
胚胎发育主要在毛囊阶段被阻止.

结论:

MT2 LTR激活对哺乳动物胚胎发育具有功能性重要性.
MT2 LTRs充当关键促进剂和增强剂,由OBOX/DUX蛋白调节.
这项研究提供了MT2元素在早期胚胎发生过程中的调节作用的直接证据.

关键词:

CP: 发育生物学梅尔维尔 (MERVEL) 是一个 MT2C_mm 在线交易 MT2_mm 在线交易内生逆转录病毒的内生逆转录病毒.编辑表观基因组编辑长终端重复重复.在植入前的胚胎.紫芽基因组激活活动

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