Rxivist logo

3D Chromatin Architecture Remodeling during Human Cardiomyocyte Differentiation Reveals A Role Of HERV-H In Demarcating Chromatin Domains

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

Posted 04 Dec 2018
bioRxiv DOI: 10.1101/485961 (published DOI: 10.1038/s41588-019-0479-7)

Dynamic restructuring of chromatin architecture has been implicated in cell-type specific gene regulatory programs; yet, how chromatin remodels during lineage specification remains to be elucidated. Through interrogating chromatin reorganization during human cardiomyocyte differentiation, we uncover dynamic chromatin interactions between genes and distal regulatory elements harboring noncoding variants associated with adult and congenital heart diseases. Unexpectedly, we also discover a new class of human pluripotent stem cell (PSC)-specific topologically associating domains (TAD) that are created by the actively transcribed endogenous retrotransposon HERV-H. Deletion or silencing of specific HERV-H elements eliminates corresponding TAD boundaries, while de novo insertion of HERV-H can introduce new chromatin domain boundaries in human PSCs. Furthermore, comparative analysis of chromatin architecture in other species that lack HERV-H sequences supports a role for actively transcribed HERV-H in demarcating human PSC-specific TADs. The biological role of HERV-H is further underscored by the observation that deletion of a specific HERV-H reduces transcription of genes upstream and facilitates cell differentiation. Overall, our results highlight a previously unrecognized role for retrotransposons in restructuring genome architecture in the human genome and delineate dynamic gene regulatory networks during cardiomyocyte development that inform how non-coding genetic variants contribute to human heart diseases.

Download data

  • Downloaded 3,317 times
  • Download rankings, all-time:
    • Site-wide: 5,013
    • In genomics: 481
  • Year to date:
    • Site-wide: 59,666
  • Since beginning of last month:
    • Site-wide: 70,804

Altmetric data


Downloads over time

Distribution of downloads per paper, site-wide


PanLingua

News