REST regulates distinct transcriptional networks in embryonic and neural 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.
Johnson
Rory
R
Stem Cell and Developmental Biology, Genome Institute of Singapore, Singapore.
Teh
Christina Hui-leng
CH
Kunarso
Galih
G
Wong
Kee Yew
KY
Srinivasan
Gopalan
G
Cooper
Megan L
ML
Volta
Manuela
M
Chan
Sarah Su-ling
SS
Lipovich
Leonard
L
Pollard
Steven M
SM
Karuturi
R Krishna Murthy
RK
Wei
Chia-lin
CL
Buckley
Noel J
NJ
Stanton
Lawrence W
LW
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
D012097:Repressor Proteins; D000099229:RE1-Silencing Transcription Factor