1. Publications

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

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.
Nat Genet. 2019-08-19;51(9):1380-1388.
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.

Related data

Available data
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Data summary
All sequencing datasets have been deposited on GEO with the accession number GSE116862.