Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Bacterial Proteins / genetics
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Bacterial Proteins / metabolism
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COS Cells
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Cell Differentiation / drug effects
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Cell Line
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Cells, Cultured
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Cerebral Cortex / physiology*
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Chlorocebus aethiops
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Chromatin / physiology
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DNA-Binding Proteins / metabolism
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Embryo, Mammalian
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Histone Deacetylase 2
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Histone Deacetylases / genetics
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Histone Deacetylases / metabolism
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Humans
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Mice
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Mice, Inbred C57BL
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NAV1.2 Voltage-Gated Sodium Channel
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Nerve Growth Factor / pharmacology
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / physiology
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Neurons / cytology
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Neurons / drug effects
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Neurons / physiology*
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PC12 Cells
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Rats
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Recombinant Fusion Proteins / metabolism
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Recombinant Proteins / metabolism
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Repressor Proteins / genetics
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Repressor Proteins / metabolism*
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Serine Endopeptidases / genetics
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Serine Endopeptidases / metabolism
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Sodium Channels / genetics
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Sodium Channels / physiology
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Transfection
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Zinc Fingers
Substances
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Bacterial Proteins
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Chromatin
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DNA-Binding Proteins
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LexA protein, Bacteria
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NAV1.2 Voltage-Gated Sodium Channel
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Nerve Tissue Proteins
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RE1-silencing transcription factor
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Recombinant Fusion Proteins
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Recombinant Proteins
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Repressor Proteins
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SCN2A protein, human
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Scn2A protein, rat
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Scn2a protein, mouse
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Sodium Channels
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Transcription Factors
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Nerve Growth Factor
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Serine Endopeptidases
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Hdac2 protein, mouse
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Hdac2 protein, rat
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Histone Deacetylase 2
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Histone Deacetylases