Polycomb complexes repress developmental regulators in murine embryonic stem cells View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2006-05

AUTHORS

Laurie A. Boyer, Kathrin Plath, Julia Zeitlinger, Tobias Brambrink, Lea A. Medeiros, Tong Ihn Lee, Stuart S. Levine, Marius Wernig, Adriana Tajonar, Mridula K. Ray, George W. Bell, Arie P. Otte, Miguel Vidal, David K. Gifford, Richard A. Young, Rudolf Jaenisch

ABSTRACT

The mechanisms by which embryonic stem (ES) cells self-renew while maintaining the ability to differentiate into virtually all adult cell types are not well understood. Polycomb group (PcG) proteins are transcriptional repressors that help to maintain cellular identity during metazoan development by epigenetic modification of chromatin structure. PcG proteins have essential roles in early embryonic development and have been implicated in ES cell pluripotency, but few of their target genes are known in mammals. Here we show that PcG proteins directly repress a large cohort of developmental regulators in murine ES cells, the expression of which would otherwise promote differentiation. Using genome-wide location analysis in murine ES cells, we found that the Polycomb repressive complexes PRC1 and PRC2 co-occupied 512 genes, many of which encode transcription factors with important roles in development. All of the co-occupied genes contained modified nucleosomes (trimethylated Lys 27 on histone H3). Consistent with a causal role in gene silencing in ES cells, PcG target genes were de-repressed in cells deficient for the PRC2 component Eed, and were preferentially activated on induction of differentiation. Our results indicate that dynamic repression of developmental pathways by Polycomb complexes may be required for maintaining ES cell pluripotency and plasticity during embryonic development. More... »

PAGES

349

Journal

TITLE

Nature

ISSUE

7091

VOLUME

441

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nature04733

DOI

http://dx.doi.org/10.1038/nature04733

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1038720785

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/16625203


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