A new family of human histone deacetylases related to Saccharomyces cerevisiae, HDA1p
byFischle W., Emiliani S., Hendzel M.J., Nagase T., Nomura N., Voelter W., Verdin E.
Fischle W., Emiliani S., Hendzel M.J., Nagase T., Nomura N., Voelter W. and Verdin E. (1999) A new family of human histone deacetylases related to Saccharomyces cerevisiae, HDA1p. Journal of Biological Chemistry 274:11713-11720
Histone deacetylases are the catalytic subunits of multiprotein complexes that are targeted to specific promoters through their interaction with sequence-specific DNA-binding factors. We have cloned and characterized a new human cDNA, HDAC-A, with homology to the yeast HDA1 familyofhistone deacetylases. Analysis of the predicted amino acid sequence of HDAC-A revealed an open reading frame of 967 amino acids containing two domains: a NH2-terminal domain with no homology to known proteins and a COOH-terminal domain with homology to known histone deacetylases(42% similarity to RPD3, 60% similarity to HDA1). Three additional human cDNAs with high homology to HDAC-A were identified in sequence data bases, indicating that HDAC-A itself is a member of a new family of human histone deacetylases. The mRNA encoding HDAC-A was differentially expressed in a variety of human tissues. The expressed protein, HDAC-Ap, exhibited histone deacetylase activity and this activity mapped to the COOH-terminal region (amino acids 495-967) with homology to HDA1p. In immunoprecipitation experiments, HDAC-A interacted specifically with several cellular proteins, indicating that it might be part of a larger multiprotein complex.