Regulation of histone deacetylase 4 and 5 and transcriptional activity by 14-3-3-dependent cellular localization.
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.
Grozinger
C M
CM
Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA.
Schreiber
S L
SL
D048948:14-3-3 Proteins; D001692:Biological Transport; D002451:Cell Compartmentation; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D028884:Karyopherins; D064326:MEF2 Transcription Factors; D008954:Models, Biological; D009154:Mutation; D018006:Myogenic Regulatory Factors; D009687:Nuclear Proteins / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D020033:Protein Isoforms / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D020539:Sequence Analysis, Protein; D014157:Transcription Factors / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase; D000099186:Histone Deacetylase 3
D048948:14-3-3 Proteins; D004268:DNA-Binding Proteins; D006655:Histone Deacetylases; D028884:Karyopherins; D064326:MEF2 Transcription Factors; D018006:Myogenic Regulatory Factors; D009687:Nuclear Proteins; D020033:Protein Isoforms; D011506:Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D014446:Tyrosine 3-Monooxygenase; D000099186:Histone Deacetylase 3; C400300:HDAC4 protein, human; C404500:HDAC5 protein, human