Corepressor-dependent silencing of chromosomal regions encoding neuronal genes.
The molecular mechanisms by which central nervous system-specific genes are expressed only in the nervous system and repressed in other tissues remain a central issue in developmental and regulatory biology. Here, we report that the zinc-finger gene-specific repressor element RE-1 silencing transcription factor/neuronal restricted silencing factor (REST/NRSF) can mediate extraneuronal restriction by imposing either active repression via histone deacetylase recruitment or long-term gene silencing using a distinct functional complex. Silencing of neuronal-specific genes requires the recruitment of an associated corepressor, CoREST, that serves as a functional molecular beacon for the recruitment of molecular machinery that imposes silencing across a chromosomal interval, including transcriptional units that do not themselves contain REST/NRSF response elements.
Lunyak
Victoria V
VV
Howard Hughes Medical Institute (HHMI), Department of Computer Science and Engineering, School of Medicine, University of California, San Diego, 9500 Gilman Drive, Room 345, La Jolla, CA 92093-0648, USA.
Burgess
Robert
R
Prefontaine
Gratien G
GG
Nelson
Charles
C
Sze
Sing-Hoi
SH
Chenoweth
Josh
J
Schwartz
Phillip
P
Pevzner
Pavel A
PA
Glass
Christopher
C
Mandel
Gail
G
Rosenfeld
Michael G
MG
D000818:Animals; D001665:Binding Sites; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D002460:Cell Line; D002868:Chromosomal Proteins, Non-Histone; D002875:Chromosomes / Q000235:genetics* / Q000378:metabolism; D002877:Chromosomes, Human / Q000235:genetics / Q000378:metabolism; D056970:Co-Repressor Proteins; D019295:Computational Biology; D018899:CpG Islands; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051783:Methyl-CpG-Binding Protein 2; D051379:Mice; D008868:Microtubule Proteins; D008957:Models, Genetic; D062551:NAV1.2 Voltage-Gated Sodium Channel; D009414:Nerve Growth Factors / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D051381:Rats; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism*; D015222:Sodium Channels / Q000235:genetics; D050777:Stathmin; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D014162:Transfection; D000099229:RE1-Silencing Transcription Factor
D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D002868:Chromosomal Proteins, Non-Histone; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; D006655:Histone Deacetylases; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051783:Methyl-CpG-Binding Protein 2; D008868:Microtubule Proteins; D062551:NAV1.2 Voltage-Gated Sodium Channel; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D012097:Repressor Proteins; D015222:Sodium Channels; D050777:Stathmin; D014157:Transcription Factors; D000099229:RE1-Silencing Transcription Factor; C497392:MECP2 protein, human; C497393:Mecp2 protein, mouse; C497394:Mecp2 protein, rat; C121019:RCOR1 protein, human; C485650:Rcor2 protein, mouse; C568251:SCN2A protein, human; C063314:STMN2 protein, human; C568253:Scn2A protein, rat; C000654500:Scn2a protein, mouse; C512849:Stmn2 protein, mouse; C512848:Stmn2 protein, rat