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REST regulates distinct transcriptional networks in embryonic and neural stem cells.

TitleREST regulates distinct transcriptional networks in embryonic and neural stem cells.
Publication TypeJournal Article
Year of Publication2008
AuthorsJohnson R, Teh CHui-leng, Kunarso G, Wong KYew, Srinivasan G, Cooper ML, Volta M, Chan SSu-ling, Lipovich L, Pollard SM, R Karuturi KMurthy, Wei C-lin, Buckley NJ, Stanton LW
JournalPLoS Biol
Date Published2008 Oct 28
KeywordsAnimals, Binding Sites, Cell Differentiation, Cell Line, Chromatin Immunoprecipitation, Embryonic Stem Cells, Fibroblasts, Gene Expression Regulation, Developmental, Gene Regulatory Networks, Mice, Neurons, NIH 3T3 Cells, Oligonucleotide Array Sequence Analysis, Repressor Proteins, Stem Cells

The maintenance of pluripotency and specification of cellular lineages during embryonic development are controlled by transcriptional regulatory networks, which coordinate specific sets of genes through both activation and repression. The transcriptional repressor RE1-silencing transcription factor (REST) plays important but distinct regulatory roles in embryonic (ESC) and neural (NSC) stem cells. We investigated how these distinct biological roles are effected at a genomic level. We present integrated, comparative genome- and transcriptome-wide analyses of transcriptional networks governed by REST in mouse ESC and NSC. The REST recruitment profile has dual components: a developmentally independent core that is common to ESC, NSC, and differentiated cells; and a large, ESC-specific set of target genes. In ESC, the REST regulatory network is highly integrated into that of pluripotency factors Oct4-Sox2-Nanog. We propose that an extensive, pluripotency-specific recruitment profile lends REST a key role in the maintenance of the ESC phenotype.

Alternate JournalPLoS Biol.
PubMed ID18959480
PubMed Central IDPMC2573930
Grant List / / Wellcome Trust / United Kingdom
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