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

doi:10.1038/s41588-019-0479-7

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 journal › Article › peer-review

30 Scopus citations

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	https://doi.org/10.1038/s41588-019-0479-7
State	Published - Sep 1 2019

ASJC Scopus subject areas

Genetics

Access to Document

10.1038/s41588-019-0479-7

Fingerprint Dive into the research topics of 'Transcriptionally active HERV-H retrotransposons demarcate topologically associating domains in human pluripotent stem cells'. Together they form a unique fingerprint.

Cite this

Zhang, Y., Li, T., Preissl, S., Amaral, M. L., Grinstein, J. D., Farah, E. N., Destici, E., Qiu, Y., Hu, R., Lee, A. Y., Chee, S., Ma, K., Ye, Z., Zhu, Q., Huang, H., Fang, R., Yu, L., Izpisua Belmonte, J. C., Wu, J., ... 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 journal › Article › peer-review

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.

@article{1e58563999554fcfaed485de56ff90b1,

title = "Transcriptionally active HERV-H retrotransposons demarcate topologically associating domains in human pluripotent stem cells",

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.",

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

note = "Funding Information: We thank S. Kuan and B. Li for sequencing and bioinformatic support. We thank E. Nostrand for RNA extraction. We thank M. Daadi (University of Texas Health Science Center at San Antonio) for providing marmoset iPSCs. We thank F. Gage (Salk Institute) for providing chimpanzee and bonobo iPSCs. This project is supported by funding from the Ludwig Institute for Cancer Research (to B.R.) and NIH (1UM1HL128773 to S.M.E., N.C.C., E.D. and B.R., and U54 DK107977 to B.R.). J.W. is the Virginia Murchison Linthicum Scholar in Medical Research. L.Y. was supported by a Hamon Center for Regenerative Science and Medicine fellowship from UT Southwestern Medical Center. S.P. was supported by a postdoctoral fellowship from the Deutsche Forschungsgemeinschaft (PR 1668/1-1). E.N.F. was supported by an NIH pre-doctoral training grant (5T32HL007444-35). M.L.A. was supported by an NIH training grant (T32GM008806-18). J.C.I.B. was supported by the Moxie Foundation.",

year = "2019",

month = sep,

day = "1",

doi = "10.1038/s41588-019-0479-7",

language = "English (US)",

volume = "51",

pages = "1380--1388",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "9",

}

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

N1 - Funding Information: We thank S. Kuan and B. Li for sequencing and bioinformatic support. We thank E. Nostrand for RNA extraction. We thank M. Daadi (University of Texas Health Science Center at San Antonio) for providing marmoset iPSCs. We thank F. Gage (Salk Institute) for providing chimpanzee and bonobo iPSCs. This project is supported by funding from the Ludwig Institute for Cancer Research (to B.R.) and NIH (1UM1HL128773 to S.M.E., N.C.C., E.D. and B.R., and U54 DK107977 to B.R.). J.W. is the Virginia Murchison Linthicum Scholar in Medical Research. L.Y. was supported by a Hamon Center for Regenerative Science and Medicine fellowship from UT Southwestern Medical Center. S.P. was supported by a postdoctoral fellowship from the Deutsche Forschungsgemeinschaft (PR 1668/1-1). E.N.F. was supported by an NIH pre-doctoral training grant (5T32HL007444-35). M.L.A. was supported by an NIH training grant (T32GM008806-18). J.C.I.B. was supported by the Moxie Foundation.

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.

UR - http://www.scopus.com/inward/record.url?scp=85071088740&partnerID=8YFLogxK

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 -