PMID- 20823235
OWN - NLM
STAT- MEDLINE
DCOM- 20101102
LR  - 20211020
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 107
IP  - 38
DP  - 2010 Sep 21
TI  - Corepressor for element-1-silencing transcription factor preferentially mediates 
      gene networks underlying neural stem cell fate decisions.
PG  - 16685-90
LID - 10.1073/pnas.0906917107 [doi]
AB  - The repressor element-1 (RE1) silencing transcription factor/neuron-restrictive 
      silencer factor (REST/NRSF) silences neuronal genes in neural stem cells (NSCs) 
      and nonneuronal cells through its role as a dynamic modular platform for 
      recruitment of transcriptional and epigenetic regulatory cofactors to 
      RE1-containing promoters. In embryonic stem cells, the REST regulatory network is 
      highly integrated with the transcriptional circuitry governing self-renewal and 
      pluripotency, although its exact functional role is unclear. The C-terminal 
      cofactor for REST, CoREST, also acts as a modular scaffold, but its cell 
      type-specific roles have not been elucidated. We used chromatin 
      immunoprecipitation-on-chip to examine CoREST and REST binding sites in NSCs and 
      their proximate progenitor species. In NSCs, we identified a larger number of 
      CoREST (1,820) compared with REST (322) target genes. The majority of these 
      CoREST targets do not contain known RE1 motifs. Notably, these CoREST target 
      genes do play important roles in pluripotency networks, in modulating NSC 
      identity and fate decisions and in epigenetic processes previously associated 
      with both REST and CoREST. Moreover, we found that NSC-mediated developmental 
      transitions were associated primarily with liberation of CoREST from promoters 
      with transcriptional repression favored in less lineage-restricted radial glia 
      and transcriptional activation favored in more lineage-restricted 
      neuronal-oligodendrocyte precursors. Clonal NSC REST and CoREST gene manipulation 
      paradigms further revealed that CoREST has largely independent and previously 
      uncharacterized roles in promoting NSC multilineage potential and modulating 
      early neural fate decisions.
FAU - Abrajano, Joseph J
AU  - Abrajano JJ
AD  - Institute for Brain Disorders and Neural Regeneration, Albert Einstein College of 
      Medicine, Bronx, NY 10461, USA.
FAU - Qureshi, Irfan A
AU  - Qureshi IA
FAU - Gokhan, Solen
AU  - Gokhan S
FAU - Molero, Aldrin E
AU  - Molero AE
FAU - Zheng, Deyou
AU  - Zheng D
FAU - Bergman, Aviv
AU  - Bergman A
FAU - Mehler, Mark F
AU  - Mehler MF
LA  - eng
GR  - R01 AG028872/AG/NIA NIH HHS/United States
GR  - NS38902/NS/NINDS NIH HHS/United States
GR  - AG027734/AG/NIA NIH HHS/United States
GR  - R01 MH066290/MH/NIMH NIH HHS/United States
GR  - AG028872/AG/NIA NIH HHS/United States
GR  - P01 AG027734/AG/NIA NIH HHS/United States
GR  - R01 NS038902/NS/NINDS NIH HHS/United States
GR  - MH66290/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100907
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Co-Repressor Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (RE1-silencing transcription factor)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Rcor2 protein, mouse)
RN  - 0 (Repressor Proteins)
SB  - IM
MH  - Animals
MH  - Binding Sites
MH  - Cell Differentiation/genetics/physiology
MH  - Cells, Cultured
MH  - Co-Repressor Proteins
MH  - Embryonic Stem Cells/*cytology/*metabolism
MH  - Gene Expression Regulation, Developmental
MH  - Gene Regulatory Networks
MH  - Mice
MH  - Nerve Tissue Proteins/antagonists & inhibitors/*genetics/*metabolism
MH  - Neurons/*cytology/*metabolism
MH  - Pluripotent Stem Cells/cytology/metabolism
MH  - Promoter Regions, Genetic
MH  - RNA, Small Interfering/genetics
MH  - Repressor Proteins/antagonists & inhibitors/*genetics/*metabolism
PMC - PMC2944745
COIS- The authors declare no conflict of interest.
EDAT- 2010/09/09 06:00
MHDA- 2010/11/03 06:00
PMCR- 2011/03/21
CRDT- 2010/09/09 06:00
PHST- 2010/09/09 06:00 [entrez]
PHST- 2010/09/09 06:00 [pubmed]
PHST- 2010/11/03 06:00 [medline]
PHST- 2011/03/21 00:00 [pmc-release]
AID - 0906917107 [pii]
AID - 200906917 [pii]
AID - 10.1073/pnas.0906917107 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2010 Sep 21;107(38):16685-90. doi: 
      10.1073/pnas.0906917107. Epub 2010 Sep 7.