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 deacetyl ation of histone proteins. The latter process is mediated by histone deacet ylases (HDACs). Previous analysis of the regulation of HDAC activity in tra nscription has focused primarily on the recruitment of HDAC proteins to spe cific promoters or chromosomal domains by association with DNA-binding prot eins. To characterize the cellular function of the recently identified HDAC 4 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 seques tration of these proteins in the cytoplasm. Loss of this interaction allows HDAC4 and HDAC5 to translocate to the nucleus, interact with HDAC3, and re press 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.