JOURNAL ARTICLE

REST regulates distinct transcriptional networks in embryonic and neural stem cells

Rory Johnson, Christina Hui-leng Teh, Galih Kunarso, Kee Yew Wong, Gopalan Srinivasan, Megan L Cooper, Manuela Volta, Sarah Su-ling Chan, Leonard Lipovich, Steven M Pollard, R Krishna Murthy Karuturi, Chia-lin Wei, Noel J Buckley, Lawrence W Stanton
PLoS Biology 2008 October 28, 6 (10): e256
18959480
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.

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