title: REST regulates distinct transcriptional networks in embryonic and neural stem cells.
abstract: 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.
authors.affiliation: Stem Cell and Developmental Biology, Genome Institute of Singapore, Singapore.
authors.forename: Rory
authors.initials: R
authors.lastname: Johnson
authors.forename: Christina Hui-leng
authors.initials: CH
authors.lastname: Teh
authors.forename: Galih
authors.initials: G
authors.lastname: Kunarso
authors.forename: Kee Yew
authors.initials: KY
authors.lastname: Wong
authors.forename: Gopalan
authors.initials: G
authors.lastname: Srinivasan
authors.forename: Megan L
authors.initials: ML
authors.lastname: Cooper
authors.forename: Manuela
authors.initials: M
authors.lastname: Volta
authors.forename: Sarah Su-ling
authors.initials: SS
authors.lastname: Chan
authors.forename: Leonard
authors.initials: L
authors.lastname: Lipovich
authors.forename: Steven M
authors.initials: SM
authors.lastname: Pollard
authors.forename: R Krishna Murthy
authors.initials: RK
authors.lastname: Karuturi
authors.forename: Chia-lin
authors.initials: CL
authors.lastname: Wei
authors.forename: Noel J
authors.initials: NJ
authors.lastname: Buckley
authors.forename: Lawrence W
authors.initials: LW
authors.lastname: Stanton
mesh_terms: D000818:Animals; D001665:Binding Sites; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D051379:Mice; D041681:NIH 3T3 Cells; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D000099229:RE1-Silencing Transcription Factor
chemical_list: D012097:Repressor Proteins; D000099229:RE1-Silencing Transcription Factor