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.

Keywords

BiologyChromatinChromatin immunoprecipitationPRC2Polycomb-group proteinsH3K4me3HistoneHistone methylationCell biologyHistone methyltransferaseHistone codeHistone H3GeneticsGeneNucleosomeTranscription factorDNA methylationPromoterGene expressionRepressor

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Publication Info

Year
2009
Type
article
Volume
23
Issue
21
Pages
2484-2489
Citations
341
Access
Closed

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Cite This

Steve Bilodeau, Michael H. Kagey, Garrett M. Frampton et al. (2009). SetDB1 contributes to repression of genes encoding developmental regulators and maintenance of ES cell state. Genes & Development , 23 (21) , 2484-2489. https://doi.org/10.1101/gad.1837309

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DOI
10.1101/gad.1837309