REST: a mammalian silencer protein that restricts sodium channel gene expression to neurons.
Expression of the type II voltage-dependent sodium channel gene is restricted to neurons by a silencer element active in nonneuronal cells. We have cloned cDNA coding for a transcription factor (REST) that binds to this silencer element. Expression of a recombinant REST protein confers the ability to silence type II reporter genes in neuronal cell types lacking the native REST protein, whereas expression of a dominant negative form of REST in nonneuronal cells relieves silencing mediated by the native protein. REST transcripts in developing mouse embryos are detected ubiquitously outside of the nervous system. We propose that expression of the type II sodium channel gene in neurons reflects a default pathway that is blocked in nonneuronal cells by the presence of REST.
Chong
J A
JA
Department of Neurobiology and Behavior, State University of New York at Stony Brook 11794-5230.
Tapia-Ramírez
J
J
Kim
S
S
Toledo-Aral
J J
JJ
Zheng
Y
Y
Boutros
M C
MC
Altshuller
Y M
YM
Frohman
M A
MA
Kraner
S D
SD
Mandel
G
G
D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D003001:Cloning, Molecular; D005314:Embryonic and Fetal Development; D005786:Gene Expression Regulation; D017403:In Situ Hybridization; D051379:Mice; D008969:Molecular Sequence Data; D009420:Nervous System / Q000196:embryology / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D009928:Organ Specificity; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae; D017386:Sequence Homology, Amino Acid; D015222:Sodium Channels / Q000096:biosynthesis*; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D016335:Zinc Fingers; D000099229:RE1-Silencing Transcription Factor
D011994:Recombinant Proteins; D012097:Repressor Proteins; D015222:Sodium Channels; D014157:Transcription Factors; D000099229:RE1-Silencing Transcription Factor