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PMID: 19884255 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

SetDB1 contributes to repression of genes encoding developmental regulators and maintenance of ES cell state.

Genes & development ·Vol. 23 ·No. 21 ·2009-11-01 ·Pages 2484-9

Bilodeau S, Kagey MH, Frampton GM, Rahl PB, Young RA

Abstract

Transcription factors that play key roles in regulating embryonic stem (ES) cell state have been identified, but the chromatin regulators that help maintain ES cells are less well understood. A high-throughput shRNA screen was used to identify novel chromatin regulators that influence ES cell state. Loss of histone H3 Lys 9 (H3K9) methyltransferases, particularly SetDB1, had the most profound effects on ES cells. Chromatin immunoprecipitation (ChIP) coupled with massively parallel DNA sequencing (ChIP-Seq) and functional analysis revealed that SetDB1 and histone H3K9-methylated nucleosomes occupy and repress genes encoding developmental regulators. These SetDB1-occupied genes are a subset of the "bivalent" genes, which contain nucleosomes with H3K4me3 (H3K4 trimethylation) and H3K27me3 modifications catalyzed by Trithorax and Polycomb group proteins, respectively. These genes are subjected to repression by both Polycomb group proteins and SetDB1, and loss of either regulator can destabilize ES cell state.

MeSH Terms
Animals Chromatin/metabolism Chromatin Immunoprecipitation Embryonic Stem Cells/cytology,enzymology Gene Expression Regulation, Developmental Histone-Lysine N-Methyltransferase Methyltransferases/metabolism Mice Nucleosomes/enzymology Protein Methyltransferases/metabolism
Chemicals
Chromatin Nucleosomes Methyltransferases Protein Methyltransferases Histone-Lysine N-Methyltransferase SETDB1 protein, mouse
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Bilodeau Steve
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA.
Kagey Michael H
Frampton Garrett M
Rahl Peter B
Young Richard A
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
1549-5477
DOI
10.1101/gad.1837309
Published
2009-11-01
Pages
2484-9
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC2779743
Subset
IM
Grants
NHGRI NIH HHS · R01 HG002668 · United States
NHGRI NIH HHS · R01 HG002668-06 · United States
CIHR · Canada
NHGRI NIH HHS · HG002668 · United States
Databases
GEO
GSE18371
External Links
PubMed source DOI: 10.1101/gad.1837309 PMC Full Text View journal details
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