Regulation of neuronal traits by a novel transcriptional complex.
The transcriptional repressor, REST, helps restrict neuronal traits to neurons by blocking their expression in nonneuronal cells. To examine the repercussions of REST expression in neurons, we generated a neuronal cell line that expresses REST conditionally. REST expression inhibited differentiation by nerve growth factor, suppressing both sodium current and neurite growth. A novel corepressor complex, CoREST/HDAC2, was shown to be required for REST repression. In the presence of REST, the CoREST/HDAC2 complex occupied the native Nav1.2 sodium channel gene in chromatin. In neuronal cells that lack REST and express sodium channels, the corepressor complex was not present on the gene. Collectively, these studies define a novel HDAC complex that is recruited by the C-terminal repressor domain of REST to actively repress genes essential to the neuronal phenotype.
Ballas
N
N
Howard Hughes Medical Institute, State University of New York, Stony Brook, 11794, USA.
Battaglioli
E
E
Atouf
F
F
Andres
M E
ME
Chenoweth
J
J
Anderson
M E
ME
Burger
C
C
Moniwa
M
M
Davie
J R
JR
Bowers
W J
WJ
Federoff
H J
HJ
Rose
D W
DW
Rosenfeld
M G
MG
Brehm
P
P
Mandel
G
G
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D019556:COS Cells; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000502:physiology*; D002522:Chlorocebus aethiops; D002843:Chromatin / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism; D004622:Embryo, Mammalian; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D062551:NAV1.2 Voltage-Gated Sodium Channel; D020932:Nerve Growth Factor / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D016716:PC12 Cells; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D015222:Sodium Channels / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D016335:Zinc Fingers; D000099160:LexA Repressor Protein; D000099229:RE1-Silencing Transcription Factor
D001426:Bacterial Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases; D062551:NAV1.2 Voltage-Gated Sodium Channel; D020932:Nerve Growth Factor; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D012097:Repressor Proteins; D012697:Serine Endopeptidases; D015222:Sodium Channels; D014157:Transcription Factors; D000099160:LexA Repressor Protein; D000099229:RE1-Silencing Transcription Factor; C568251:SCN2A protein, human; C568253:Scn2A protein, rat; C000654500:Scn2a protein, mouse; C533424:Hdac2 protein, mouse; C533426:Hdac2 protein, rat