Regulation of neuronal traits by a novel transcriptional complex

Nurit Ballas; Elena Battaglioli; Fouad Atouf; Maria E. Andres; Josh Chenoweth; Mary E. Anderson; Corinna Burger; Mariko Moniwa; James R. Davie; William J. Bowers; Howard J. Federoff; David W. Rose; Michael G. Rosenfeld; Paul Brehm; Gail Mandel

doi:10.1016/S0896-6273(01)00371-3

Regulation of neuronal traits by a novel transcriptional complex

Nurit Ballas, Elena Battaglioli, Fouad Atouf, Maria E. Andres, Josh Chenoweth, Mary E. Anderson, Corinna Burger, Mariko Moniwa, James R. Davie, William J. Bowers, Howard J. Federoff, David W. Rose, Michael G. Rosenfeld, Paul Brehm, Gail Mandel

Research output: Contribution to journal › Article › peer-review

361 Scopus citations

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.

Original language	English (US)
Pages (from-to)	353-365
Number of pages	13
Journal	Neuron
Volume	31
Issue number	3
DOIs	https://doi.org/10.1016/S0896-6273(01)00371-3
State	Published - Aug 16 2001
Externally published	Yes

ASJC Scopus subject areas

General Neuroscience

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10.1016/S0896-6273(01)00371-3

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@article{62b31410c49c47adb191ada36a99a3ff,

title = "Regulation of neuronal traits by a novel transcriptional complex",

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.",

author = "Nurit Ballas and Elena Battaglioli and Fouad Atouf and Andres, {Maria E.} and Josh Chenoweth and Anderson, {Mary E.} and Corinna Burger and Mariko Moniwa and Davie, {James R.} and Bowers, {William J.} and Federoff, {Howard J.} and Rose, {David W.} and Rosenfeld, {Michael G.} and Paul Brehm and Gail Mandel",

note = "Funding Information: We thank Joan Speh for help with the immunocytochemistry and graphics, Weiyan Li for help with statistical analysis, and Dr. Joseph Koipally, Dr. Katia Georgopoulos, and Dr. Stuart Schreiber for sharing unpublished results. The work was supported by grants from the NIH (NS22518) and the McKnight Foundation to G.M., NIH DK54802 (D.W.R.), NIH, CAPCURE, and California Cancer Research Program (M.G.R.), Canadian Institute of Health Research Grant MT-9186 (J.D.), NIH Grant GM 50224-S1 (N.B.), AFAR Research Grant (W.J.B.), and NIH P30 AG18254 (H.J.F.). G.M. and M.G.R. are Investigators of the Howard Hughes Medical Institute.",

year = "2001",

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doi = "10.1016/S0896-6273(01)00371-3",

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T1 - Regulation of neuronal traits by a novel transcriptional complex

AU - Ballas, Nurit

AU - Battaglioli, Elena

AU - Atouf, Fouad

AU - Andres, Maria E.

AU - Chenoweth, Josh

AU - Anderson, Mary E.

AU - Burger, Corinna

AU - Moniwa, Mariko

AU - Davie, James R.

AU - Bowers, William J.

AU - Federoff, Howard J.

AU - Rose, David W.

AU - Rosenfeld, Michael G.

AU - Brehm, Paul

AU - Mandel, Gail

N1 - Funding Information: We thank Joan Speh for help with the immunocytochemistry and graphics, Weiyan Li for help with statistical analysis, and Dr. Joseph Koipally, Dr. Katia Georgopoulos, and Dr. Stuart Schreiber for sharing unpublished results. The work was supported by grants from the NIH (NS22518) and the McKnight Foundation to G.M., NIH DK54802 (D.W.R.), NIH, CAPCURE, and California Cancer Research Program (M.G.R.), Canadian Institute of Health Research Grant MT-9186 (J.D.), NIH Grant GM 50224-S1 (N.B.), AFAR Research Grant (W.J.B.), and NIH P30 AG18254 (H.J.F.). G.M. and M.G.R. are Investigators of the Howard Hughes Medical Institute.

PY - 2001/8/16

Y1 - 2001/8/16

N2 - 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.

AB - 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.

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JO - Neuron

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Regulation of neuronal traits by a novel transcriptional complex

Abstract

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