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

   January 23rd, 2020 at 3:08pm



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.


Zhang Y  •  Li T  •  Preissl S  •  Amaral ML  •  Grinstein JD  •  Farah EN  •  Destici E  •  Qiu Y  •  Hu R  •  Lee AY  •  Chee S  •  Ma K  •  Ye Z  •  Zhu Q  •  Huang H  •  Fang R  •  Yu L  •  Izpisua Belmonte JC  •  Wu J  •  Evans SM  •  Chi NC  •  Ren B



Nature genetics



September 2019