Isolation and Characterization of cDNAs Corresponding to an Additional Member of the Human Histone Deacetylase Gene Family*

Several human cDNAs encoding a histone deacetylase protein, HDAC3, have been isolated. Analysis of the predicted amino acid sequence of HDAC3 revealed an open reading frame of 428 amino acids with a predicted molecular mass of 49 kDa. The HDAC3 protein is 50% identical in DNA sequence and 53% identical in protein sequence compared with the previously cloned human HDAC1. Comparison of the HDAC3 sequence with human HDAC2 also yielded similar results, with 51% identity in DNA sequence and 52% identity in protein sequence. The expressed HDAC3 protein is functionally active because it possesses histone deacetylase activity, represses transcription when tethered to a promoter, and binds transcription factor YY1. Similar to HDAC1 and HDAC2, HDAC3 is ubiquitously expressed in many different cell types.

[1]  K. Struhl,et al.  The histone deacetylase RPD3 counteracts genomic silencing in Drosophila and yeast , 1996, Nature.

[2]  J. Davie,et al.  Histone deacetylase is a component of the internal nuclear matrix. , 1991, The Journal of biological chemistry.

[3]  D. Ron,et al.  pGSTag--a versatile bacterial expression plasmid for enzymatic labeling of recombinant proteins. , 1992, BioTechniques.

[4]  Andrew J. Bannister,et al.  The TAFII250 Subunit of TFIID Has Histone Acetyltransferase Activity , 1996, Cell.

[5]  B. Neel,et al.  Solubilization and purification of enzymatically active glutathione S-transferase (pGEX) fusion proteins. , 1993, Analytical biochemistry.

[6]  I. Sadowski,et al.  GAL4 fusion vectors for expression in yeast or mammalian cells. , 1992, Gene.

[7]  B. Howard,et al.  The Transcriptional Coactivators p300 and CBP Are Histone Acetyltransferases , 1996, Cell.

[8]  M. Vidal,et al.  RPD3 encodes a second factor required to achieve maximum positive and negative transcriptional states in Saccharomyces cerevisiae , 1991, Molecular and cellular biology.

[9]  M. Ptashne,et al.  A vector for expressing GAL4(1-147) fusions in mammalian cells. , 1989, Nucleic acids research.

[10]  C. Allis,et al.  Special HATs for special occasions: linking histone acetylation to chromatin assembly and gene activation. , 1996, Current opinion in genetics & development.

[11]  D. Reinberg,et al.  Histone Deacetylases and SAP18, a Novel Polypeptide, Are Components of a Human Sin3 Complex , 1997, Cell.

[12]  L. Chin,et al.  Role for N-CoR and histone deacetylase in Sin3-mediated transcriptional repression , 1997, nature.

[13]  C. Glass,et al.  A complex containing N-CoR, mSln3 and histone deacetylase mediates transcriptional repression , 1997, nature.

[14]  Yang Shi,et al.  Transcriptional repression by YY1, a human GLI-Krüippel-related protein, and relief of repression by adenovirus E1A protein , 1991, Cell.

[15]  B. Luckow,et al.  CAT constructions with multiple unique restriction sites for the functional analysis of eukaryotic promoters and regulatory elements , 1987, Nucleic Acids Res..

[16]  J. Sambrook,et al.  Molecular Cloning: A Laboratory Manual , 2001 .

[17]  Andrew J. Bannister,et al.  The CBP co-activator is a histone acetyltransferase , 1996, Nature.

[18]  A. van der Eb,et al.  A new technique for the assay of infectivity of human adenovirus 5 DNA. , 1973, Virology.

[19]  J. Davie Histone modifications, chromatin structure, and the nuclear matrix , 1996, Journal of cellular biochemistry.

[20]  Wen‐Ming Yang,et al.  Transcriptional repression by YY1 is mediated by interaction with a mammalian homolog of the yeast global regulator RPD3. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[21]  G. Brosch,et al.  Identification of maize histone deacetylase HD2 as an acidic nucleolar phosphoprotein. , 1997, Science.

[22]  Wen‐Ming Yang,et al.  Histone Deacetylases Associated with the mSin3 Corepressor Mediate Mad Transcriptional Repression , 1997, Cell.

[23]  C. Allis,et al.  Transcription-linked acetylation by Gcn5p of histones H3 and H4 at specific lysines , 1996, Nature.

[24]  John M. Barrie,et al.  The World Wide Web as an Instructional Tool , 1996, Science.

[25]  B. Howard,et al.  Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells , 1982, Molecular and cellular biology.

[26]  S. Schreiber,et al.  Nuclear Receptor Repression Mediated by a Complex Containing SMRT, mSin3A, and Histone Deacetylase , 1997, Cell.

[27]  R. Timpl,et al.  Cloning and chromosomal location of human alpha 1(XVI) collagen. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[28]  Stuart L Schreiber,et al.  Histone Deacetylase Activity Is Required for Full Transcriptional Repression by mSin3A , 1997, Cell.

[29]  S. Schreiber,et al.  A Mammalian Histone Deacetylase Related to the Yeast Transcriptional Regulator Rpd3p , 1996, Science.

[30]  C. Allis,et al.  Tetrahymena Histone Acetyltransferase A: A Homolog to Yeast Gcn5p Linking Histone Acetylation to Gene Activation , 1996, Cell.

[31]  C. Liu,et al.  Characterization of a novel 350-kilodalton nuclear phosphoprotein that is specifically involved in mitotic-phase progression , 1995, Molecular and cellular biology.

[32]  M. Grunstein,et al.  HDA1 and RPD3 are members of distinct yeast histone deacetylase complexes that regulate silencing and transcription. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[33]  G. Jenster,et al.  Steroid receptor induction of gene transcription: a two-step model. , 1997, Proceedings of the National Academy of Sciences of the United States of America.