Transcriptionally active HERV-H retrotransposons demarcate topologically associating domains in human pluripotent stem cells.
Journal
Nature genetics
ISSN: 1546-1718
Titre abrégé: Nat Genet
Pays: United States
ID NLM: 9216904
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
31
01
2019
accepted:
09
07
2019
pubmed:
21
8
2019
medline:
24
1
2020
entrez:
21
8
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31427791
doi: 10.1038/s41588-019-0479-7
pii: 10.1038/s41588-019-0479-7
pmc: PMC6722002
mid: NIHMS1534161
doi:
Substances chimiques
Chromatin
0
Retroelements
0
Transcription Factors
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1380-1388Subventions
Organisme : NIGMS NIH HHS
ID : T32 GM008806
Pays : United States
Organisme : NHLBI NIH HHS
ID : UM1 HL128773
Pays : United States
Organisme : NIDDK NIH HHS
ID : U54 DK107977
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL131003
Pays : United States
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