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

Proc Natl Acad Sci U S A
Authors
Keywords
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 with14-3-3 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.

Year of Publication
2000
Journal
Proc Natl Acad Sci U S A
Volume
97
Issue
14
Pages
7835-40
Date Published
2000 Jul 05
ISSN
0027-8424
DOI
10.1073/pnas.140199597
PubMed ID
10869435
PubMed Central ID
PMC16631
Links
Grant list
R01 GM038627 / GM / NIGMS NIH HHS / United States
R37 GM038627 / GM / NIGMS NIH HHS / United States
GM38627 / GM / NIGMS NIH HHS / United States