Acetylated histones yield a favorable environment for the transcription of genes; acetylation allows for greater accessibility to gene promoters by transcription factors. On the other hand, histone deacetylases (HDACs) inhibit transcription by limiting accessibility to chromatin. HDACs bind to several transcription factors including the MEF2 family of transcription factors, which are involved in muscle cell differentiation. Grozinger and Scheiber investigate the regulation of HDAC4 and HDAC5, and observe that 14-3-3 proteins, which bind to phosphoserine residues, mediate the localization of HDACs within the cell. Immunocomplexes of overexpressed HDAC4 and HDAC5 contained 14-3-3 proteins, whereas overexpression of HDAC1, representing a different class of HDAC, did not. Fluorescence assays revealed that overexpressed HDAC4 localized to the nucleus, but in the presence of overexpressed 14-3-3β, HDAC4 remained in the cytoplasm. The association of 14-3-3 and HDAC4 was phosphoserine-dependent, and prevented the ability of importin α, a nuclear translocator protein, to bind HDAC4. Finally, increased nuclear localization of HDAC4 correlated with decreased MEF2-dependent transcription. Thus, these results suggest that 14-3-3 proteins can function to regulate transcription by associating with HDAC proteins.
Grozinger, C.M., and Schreiber, S.L. (2000) Regulation of histone deacetylase 4 and 5 and transcriptional activity by 14-3-3-dependent cellular localization. Proc. Natl. Acad. Sci. U.S.A. 97: 7835-7840. [Abstract] [Full Text]