Characterization of a human RPD3 ortholog, HDAC3.
Histone acetylation levels in cells result from a dynamic equilibrium between competing histone acetylases and deacetylases. Changes in histone acetylation levels occur during both transcriptional activation and silencing. Cloning of the cDNA for a human histone deacetylase (HDAC1) has shown that it represents a human ortholog of the yeast transcriptional regulator RPD3. We have screened the expressed sequence tag database (National Center for Biotechnology Information) with the yeast RPD3 sequence and identified a human ortholog of RPD3, HDAC3. This cDNA encodes a protein of 428 amino acids with 58% sequence identity with HDAC1p. By using a specific polyclonal antiserum recognizing the C-terminal domain of HDAC3p and Western blotting, we detected a single approximately 49-kDa band in several tumor cell lines. HDAC3p is expressed predominantly in the nuclear compartment. Immunoprecipitation experiments with either an antiserum against HDAC3p or an anti-FLAG antiserum and a flagged HDAC3 cDNA showed that HDAc3p exhibits deacetylase activity both on free histones and on purified nucleosomes. This deacetylase activity is inhibited by trichostatin, trapoxin, and butyrate in vitro to the same degree as the deacetylase activity associated to HDAC1p. These observations identify another member of a growing family of human HDAC genes.
Emiliani
S
S
Picower Institute for Medical Research, Manhasset, NY 11030, USA.
Fischle
W
W
Van Lint
C
C
Al-Abed
Y
Y
Verdin
E
E
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001483:Base Sequence; D002087:Butyrates / Q000494:pharmacology; D020148:Butyric Acid; D018076:DNA, Complementary / Q000235:genetics; D015870:Gene Expression; D015723:Gene Library; D056284:Histone Deacetylase 1; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics* / Q000302:isolation & purification; D009707:Nucleosomes / Q000378:metabolism*; D010455:Peptides; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000235:genetics; D000099186:Histone Deacetylase 3
D000900:Anti-Bacterial Agents; D002087:Butyrates; D020148:Butyric Acid; D018076:DNA, Complementary; D056284:Histone Deacetylase 1; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases; D006657:Histones; D006877:Hydroxamic Acids; D009687:Nuclear Proteins; D009707:Nucleosomes; D010455:Peptides; D014157:Transcription Factors; D000099186:Histone Deacetylase 3; C067070:trapoxin A; C012589:trichostatin A; C110550:HDAC1 protein, human