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 language | English (US) |
|---|---|
| Pages (from-to) | 1380-1388 |
| Number of pages | 9 |
| Journal | Nature genetics |
| Volume | 51 |
| Issue number | 9 |
| DOIs | |
| State | Published - Sep 1 2019 |
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ASJC Scopus subject areas
- Genetics
Cite this
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 journal › Article
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TY - JOUR
T1 - Transcriptionally active HERV-H retrotransposons demarcate topologically associating domains in human pluripotent stem cells
AU - Zhang, Yanxiao
AU - Li, Ting
AU - Preissl, Sebastian
AU - Amaral, Maria Luisa
AU - Grinstein, Jonathan D.
AU - Farah, Elie N.
AU - Destici, Eugin
AU - Qiu, Yunjiang
AU - Hu, Rong
AU - Lee, Ah Young
AU - Chee, Sora
AU - Ma, Kaiyue
AU - Ye, Zhen
AU - Zhu, Quan
AU - Huang, Hui
AU - Fang, Rongxin
AU - Yu, Leqian
AU - Izpisua Belmonte, Juan Carlos
AU - Wu, Jun
AU - Evans, Sylvia M.
AU - Chi, Neil C.
AU - Ren, Bing
PY - 2019/9/1
Y1 - 2019/9/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=85071088740&partnerID=8YFLogxK
U2 - 10.1038/s41588-019-0479-7
DO - 10.1038/s41588-019-0479-7
M3 - Article
C2 - 31427791
AN - SCOPUS:85071088740
VL - 51
SP - 1380
EP - 1388
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 9
ER -