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PMID: 9501169 Published · ppublish English Comparative Study Journal Article Research Support, U.S. Gov't, P.H.S.

Characterization of a human RPD3 ortholog, HDAC3.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 95 ·No. 6 ·1998-03-17 ·Pages 2795-800

Emiliani S, Fischle W, Van Lint C, Al-Abed Y, Verdin E

Abstract

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.

MeSH Terms
Amino Acid Sequence Anti-Bacterial Agents/pharmacology Base Sequence Butyrates/pharmacology Butyric Acid DNA, Complementary/genetics Gene Expression Gene Library Histone Deacetylase 1 Histone Deacetylase Inhibitors Histone Deacetylases/genetics,isolation & purification,metabolism Histones/metabolism Humans Hydroxamic Acids/pharmacology Molecular Sequence Data Nuclear Proteins/genetics,isolation & purification Nucleosomes/metabolism Peptides Sequence Homology, Amino Acid Transcription Factors/genetics
Chemicals
Anti-Bacterial Agents Butyrates DNA, Complementary Histone Deacetylase Inhibitors Histones Hydroxamic Acids Nuclear Proteins Nucleosomes Peptides Transcription Factors Butyric Acid trapoxin A trichostatin A HDAC1 protein, human Histone Deacetylase 1 Histone Deacetylases histone deacetylase 3
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Emiliani S
Picower Institute for Medical Research, Manhasset, NY 11030, USA.
Fischle W
Van Lint C
Al-Abed Y
Verdin E
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.95.6.2795
Published
1998-03-17
Pages
2795-800
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC19648
Subset
IM
Grants
NIGMS NIH HHS · R01 GM051671 · United States
NIGMS NIH HHS · GM51671 · United States
Databases
GENBANK
AF039703
External Links
PubMed source DOI: 10.1073/pnas.95.6.2795 PMC Full Text View journal details
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