Format

Send to

Choose Destination
Nat Genet. 2019 Sep;51(9):1380-1388. doi: 10.1038/s41588-019-0479-7. Epub 2019 Aug 19.

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

Author information

1
Ludwig Institute for Cancer Research, La Jolla, CA, USA.
2
Department of Medicine, Division of Cardiology, University of California San Diego, La Jolla, CA, USA.
3
Center for Epigenomics, Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.
4
Bioinformatics and Systems Biology Graduate Program, University of California San Diego, La Jolla, CA, USA.
5
Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, CA, USA.
6
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
7
Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
8
Salk Institute for Biological Studies, San Diego, CA, USA.
9
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
10
Department of Medicine, Division of Cardiology, University of California San Diego, La Jolla, CA, USA. nchi@ucsd.edu.
11
Institute of Genomic Medicine, School of Medicine, University of California San Diego, La Jolla, CA, USA. nchi@ucsd.edu.
12
Ludwig Institute for Cancer Research, La Jolla, CA, USA. biren@ucsd.edu.
13
Center for Epigenomics, Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA. biren@ucsd.edu.
14
Institute of Genomic Medicine, School of Medicine, University of California San Diego, La Jolla, CA, USA. biren@ucsd.edu.
15
Moores Cancer Center, School of Medicine, University of California San Diego, La Jolla, CA, USA. biren@ucsd.edu.

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.

PMID:
31427791
PMCID:
PMC6722002
[Available on 2020-02-19]
DOI:
10.1038/s41588-019-0479-7

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center