Regulation of histone deacetylase 4 and 5 and transcriptional activity by 14-3-3-dependent cellular localization

Christina M. Grozinger, Stuart L. Schreiber

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452 Citations (Scopus)

Abstract

Transcription is controlled in part by the dynamic acetylation and deacetylation of histone proteins. The latter process is mediated by histone deacetylases (HDACs). Previous analysis of the regulation of HDAC activity in transcription has focused primarily on the recruitment of HDAC proteins to specific promoters or chromosomal domains by association with DNA-binding proteins. To characterize the cellular function of the recently identified HDAC4 and HDAC5 proteins, complexes were isolated by immunoprecipitation. Both HDACs were found to interact with 14-3-3 proteins at three phosphorylation sites. The association of 14-3-3 with HDAC4 and HDAC5 results in the sequestration of these proteins in the cytoplasm. Loss of this interaction allows HDAC4 and HDAC5 to translocate to the nucleus, interact with HDAC3, and repress gene expression. Regulation of the cellular localization of HDAC4 and HDAC5 by 14-3-3 represents a mechanism for controlling the transcriptional activity of these class II HDAC proteins.

Original languageEnglish (US)
Pages (from-to)7835-7840
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number14
DOIs
StatePublished - Jul 5 2000

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Histone Deacetylases
Proteins
14-3-3 Proteins
DNA-Binding Proteins
Acetylation
Immunoprecipitation
Histones
Cytoplasm
Phosphorylation
Gene Expression

All Science Journal Classification (ASJC) codes

  • General

Cite this

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abstract = "Transcription is controlled in part by the dynamic acetylation and deacetylation of histone proteins. The latter process is mediated by histone deacetylases (HDACs). Previous analysis of the regulation of HDAC activity in transcription has focused primarily on the recruitment of HDAC proteins to specific promoters or chromosomal domains by association with DNA-binding proteins. To characterize the cellular function of the recently identified HDAC4 and HDAC5 proteins, complexes were isolated by immunoprecipitation. Both HDACs were found to interact with 14-3-3 proteins at three phosphorylation sites. The association of 14-3-3 with HDAC4 and HDAC5 results in the sequestration of these proteins in the cytoplasm. Loss of this interaction allows HDAC4 and HDAC5 to translocate to the nucleus, interact with HDAC3, and repress gene expression. Regulation of the cellular localization of HDAC4 and HDAC5 by 14-3-3 represents a mechanism for controlling the transcriptional activity of these class II HDAC proteins.",
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AU - Schreiber, Stuart L.

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