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HERV-H逆转录转座子功能获揭示
作者:小柯机器人 发布时间:2019/8/20 14:43:42

美国加州大学圣地亚哥分校任兵和Neil C.Chi研究组合作发现,转录活跃的HERV-H逆转录转座子,能够在人类多潜能干细胞中划分拓扑相关结构域。相关论文于8月19日在线发表于《自然—遗传学》上。

通过研究人类多潜能干细胞(hPSC)分化过程中的染色质重组,该课题组发现灵长类动物特异的内源性逆转录转座子HERV-H在hPSC中建立拓扑相关结构域(TADs)方面的作用。敲除这些HERV-H元件会消除其对应的TAD边界并下调上游基因的转录,而HERV-H元件的从头插入会形成新的TAD边界。HERV-H建立TAD边界的能力依赖于高转录水平,因为HERV-H元件的转录抑制,阻止了边界的形成。HERV-H元件形成新的TAD边界能力并不局限在hPSC分化过程中,因为这些主动转录的HERV-H元件及其对应的TAD边界也出现在其他灵长类动物的多潜能干细胞中,但不出现在缺乏HERV-H元件的亲缘关系较远的物种中。总的来说,他们的结果为逆转录转座子在积极塑造细胞类型和物种特异性染色质结构中提供了直接证据。

据介绍,染色质的结构已经涉及到细胞类型特异性基因调控程序,但染色质在发育过程中如何重组仍有待充分阐明。

附:英文原文

Title: Transcriptionally active HERV-H retrotransposons demarcate topologically associating domains in human pluripotent stem cells

Author: Yanxiao Zhang, Ting Li, Sebastian Preissl, Maria Luisa Amaral, Jonathan D. Grinstein, Elie N. Farah, Eugin Destici, Yunjiang Qiu, Rong Hu, Ah Young Lee, Sora Chee, Kaiyue Ma, Zhen Ye, Quan Zhu, Hui Huang, Rongxin Fang, Leqian Yu, Juan Carlos Izpisua Belmonte, Jun Wu, Sylvia M. Evans, Neil C. Chi, Bing Ren 

Issue&Volume: 19 August 2019

Abstract: Chromatin architecture has been implicated in cell type-specific gene regulatory programs, yet how chromatin remodels during development remains to be fully elucidated. Here, by interrogating chromatin reorganization during human pluripotent stem cell (hPSC) differentiation, we discover a role for the primate-specific endogenous retrotransposon human endogenous retrovirus subfamily H (HERV-H) in creating topologically associating domains (TADs) in hPSCs. Deleting these HERV-H elements eliminates their corresponding TAD boundaries and reduces the transcription of upstream genes, while de novo insertion of HERV-H elements can introduce new TAD boundaries. The ability of HERV-H to create TAD boundaries depends on high transcription, as transcriptional repression of HERV-H elements prevents the formation of boundaries. This ability is not limited to hPSCs, as these actively transcribed HERV-H elements and their corresponding TAD boundaries also appear in pluripotent stem cells from other hominids but not in more distantly related species lacking HERV-H elements. Overall, our results provide direct evidence for retrotransposons in actively shaping cell type- and species-specific chromatin architecture.

DOI: https://doi.org/10.1038/s41588-019-0479-7

Source: https://www.nature.com/articles/s41588-019-0479-7

期刊信息

Nature Genetics:《自然—遗传学》,创刊于1992年。隶属于施普林格·自然出版集团,最新IF:25.455
官方网址:https://www.nature.com/ng/
投稿链接:https://mts-ng.nature.com/cgi-bin/main.plex