Format

Send to

Choose Destination
Genes Dev. 2016 May 1;30(9):1101-15. doi: 10.1101/gad.275685.115. Epub 2016 Apr 28.

The pluripotency factor Nanog regulates pericentromeric heterochromatin organization in mouse embryonic stem cells.

Author information

1
Epigenetics Programme, The Babraham Institute, Cambridge CB22 3AT, United Kingdom;
2
Program in Genetics and Genome Biology, Hospital for Sick Children, Toronto, Ontario MSG 1L7, Canada; Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada;
3
Program in Genetics and Genome Biology, Hospital for Sick Children, Toronto, Ontario MSG 1L7, Canada;
4
Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, Ontario M5G 1L7, Canada; Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada;
5
MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh EH16 4UU, United Kingdom;
6
Nuclear Dynamics Programme, The Babraham Institute, Cambridge, CB22 3AT, United Kingdom;
7
Department of Kidney Development, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto 860-0811, Japan;
8
Epigenetics Programme, The Babraham Institute, Cambridge CB22 3AT, United Kingdom; Centre for Trophoblast Research, University of Cambridge, Cambridge CB2 3EG, United Kingdom; Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 1QR, United Kingdom.

Abstract

An open and decondensed chromatin organization is a defining property of pluripotency. Several epigenetic regulators have been implicated in maintaining an open chromatin organization, but how these processes are connected to the pluripotency network is unknown. Here, we identified a new role for the transcription factor NANOG as a key regulator connecting the pluripotency network with constitutive heterochromatin organization in mouse embryonic stem cells. Deletion of Nanog leads to chromatin compaction and the remodeling of heterochromatin domains. Forced expression of NANOG in epiblast stem cells is sufficient to decompact chromatin. NANOG associates with satellite repeats within heterochromatin domains, contributing to an architecture characterized by highly dispersed chromatin fibers, low levels of H3K9me3, and high major satellite transcription, and the strong transactivation domain of NANOG is required for this organization. The heterochromatin-associated protein SALL1 is a direct cofactor for NANOG, and loss of Sall1 recapitulates the Nanog-null phenotype, but the loss of Sall1 can be circumvented through direct recruitment of the NANOG transactivation domain to major satellites. These results establish a direct connection between the pluripotency network and chromatin organization and emphasize that maintaining an open heterochromatin architecture is a highly regulated process in embryonic stem cells.

KEYWORDS:

embryonic stem cells; heterochromatin; nuclear organization; pluripotency

PMID:
27125671
PMCID:
PMC4863740
DOI:
10.1101/gad.275685.115
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center