Enzymatic activity associated with class II HDACs is dependent on a multiprotein complex containing HDAC3 and SMRT/N-CoR.
Histone deacetylases (HDACs) play a key role in regulating eukaryotic gene expression. The HDAC domain, homologous to the yeast repressors RPD3 and HDA1, is considered necessary and sufficient for enzymatic activity. Here, we show that the catalytic domain of HDAC4 interacts with HDAC3 via the transcriptional corepressor N-CoR/SMRT. All experimental conditions leading to the suppression of HDAC4 binding to SMRT/N-CoR and to HDAC3 result in the loss of enzymatic activity associated with HDAC4. In vitro reconstitution experiments indicate that HDAC4 and other class II HDACs are inactive in the context of the SMRT/N-CoR-HDAC3 complex and do not contribute to its enzymatic activity. These observations indicate that class II HDACs regulate transcription by bridging the enzymatically active SMRT/N-CoR-HDAC3 complex and select transcription factors independently of any intrinsic HDAC activity.
Fischle
Wolfgang
W
Gladstone Institute of Virology and Immunology, University of California, San Francisco, San Francisco, CA 94141, USA.
Dequiedt
Franck
F
Hendzel
Michael J
MJ
Guenther
Matthew G
MG
Lazar
Mitchell A
MA
Voelter
Wolfgang
W
Verdin
Eric
E
D000595:Amino Acid Sequence; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D006367:HeLa Cells; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D056985:Nuclear Receptor Co-Repressor 2; D011485:Protein Binding; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D000099186:Histone Deacetylase 3
D004268:DNA-Binding Proteins; D006655:Histone Deacetylases; D056985:Nuclear Receptor Co-Repressor 2; D012097:Repressor Proteins; D000099186:Histone Deacetylase 3; C539130:NCOR2 protein, human; C400300:HDAC4 protein, human; C404500:HDAC5 protein, human