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. EvansNeil C. Chi, Bing Ren

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)1380-1388
Number of pages9
JournalNature genetics
Volume51
Issue number9
DOIs
StatePublished - Sep 1 2019

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Endogenous Retroviruses
Pluripotent Stem Cells
Retroelements
Chromatin
Hominidae
Regulator Genes
Primates
Cell Differentiation

ASJC Scopus subject areas

  • Genetics

Cite this

Zhang, Y., Li, T., Preissl, S., Amaral, M. L., Grinstein, J. D., Farah, E. N., ... Ren, B. (2019). Transcriptionally active HERV-H retrotransposons demarcate topologically associating domains in human pluripotent stem cells. Nature genetics, 51(9), 1380-1388. https://doi.org/10.1038/s41588-019-0479-7

Transcriptionally active HERV-H retrotransposons demarcate topologically associating domains in human pluripotent stem cells. / Zhang, Yanxiao; Li, Ting; Preissl, Sebastian; Amaral, Maria Luisa; Grinstein, Jonathan D.; Farah, Elie N.; Destici, Eugin; Qiu, Yunjiang; Hu, Rong; Lee, Ah Young; Chee, Sora; Ma, Kaiyue; Ye, Zhen; Zhu, Quan; Huang, Hui; Fang, Rongxin; Yu, Leqian; Izpisua Belmonte, Juan Carlos; Wu, Jun; Evans, Sylvia M.; Chi, Neil C.; Ren, Bing.

In: Nature genetics, Vol. 51, No. 9, 01.09.2019, p. 1380-1388.

Research output: Contribution to journalArticle

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 2019, 'Transcriptionally active HERV-H retrotransposons demarcate topologically associating domains in human pluripotent stem cells', Nature genetics, vol. 51, no. 9, pp. 1380-1388. https://doi.org/10.1038/s41588-019-0479-7
Zhang, Yanxiao ; Li, Ting ; Preissl, Sebastian ; Amaral, Maria Luisa ; Grinstein, Jonathan D. ; Farah, Elie N. ; Destici, Eugin ; Qiu, Yunjiang ; Hu, Rong ; Lee, Ah Young ; Chee, Sora ; Ma, Kaiyue ; Ye, Zhen ; Zhu, Quan ; Huang, Hui ; Fang, Rongxin ; Yu, Leqian ; Izpisua Belmonte, Juan Carlos ; Wu, Jun ; Evans, Sylvia M. ; Chi, Neil C. ; Ren, Bing. / Transcriptionally active HERV-H retrotransposons demarcate topologically associating domains in human pluripotent stem cells. In: Nature genetics. 2019 ; Vol. 51, No. 9. pp. 1380-1388.
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