Human Histone Deacetylase 2,HDAC2(HumanRPD3), Is Localized to 6q21 by Radiation Hybrid Mapping

Betz, Regina C.; Gray, Steven G.; Ekström, Christina; Ekström, Tomas J.

doi:10.1006/geno.1998.5435

Cited by 15 publications

(8 citation statements)

References 5 publications

(2 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…HDAC8 maps to the X chromosome at position Xq21.2-Xq21.3. The other class I deacetylases, HDAC1, HDAC2 and HDAC3, map to chromosomal positions 1p34, 6q21 and 5q31 respectively [38,39], making HDAC8 the only known example of an X-linked deacetylase. It is interesting to note that the inactive X chromosome in female mammals is distinguished by a lack of histone H4 acetylation, and hypoacetylation of specific promoters has been shown to be essential for X-inactivation [40][41][42].…”

Section: Discussionmentioning

confidence: 99%

Cloning and characterization of a novel human histone deacetylase, HDAC8

Buggy

Sideris

Mak

et al. 2000

Biochemical Journal

155

101

View full text Add to dashboard Cite

Histone deacetylases (HDACs) are a growing family of enzymes implicated in transcriptional regulation by affecting the acetylation state of core histones in the nucleus of cells. HDACs are known to have key roles in the regulation of cell proliferation [Brehm, Miska, McCance, Reid, Bannister and Kouzarides (1998) Nature (London) 391, 597-600], and aberrant recruitment of an HDAC complex has been shown to be a key step in the mechanism of cell transformation in acute promyelocytic leukaemia [Grignani, De Matteis, Nervi, Tomassoni, Gelmetti, Cioce, Fanelli, Ruthardt, Ferrara, Zamir et al. (1998) Nature (London) 391, 815-818; Lin, Nagy, Inoue, Shao, Miller and Evans (1998), Nature (London) 391, 811-814]. Here we present the complete nucleotide sequence of a cDNA clone, termed HDAC8, that encodes a protein product with similarity to the RPD3 class (I) of HDACs. The predicted 377-residue HDAC8 product contains a shorter C-terminal extension relative to other members of its class. After expression in two cell systems, immunopurified HDAC8 is shown to possess trichostatin A- and sodium butyrate-inhibitable HDAC activity on histone H4 peptide substrates as well as on core histones. Expression profiling reveals the expression of HDAC8 to various degrees in every tissue tested and also in several tumour lines. Mutation of two adjacent histidine residues within the predicted active site severely decreases activity, confirming these residues as important for HDAC8 enzyme activity. Finally, linkage analysis after radiation hybrid mapping has localized HDAC8 to chromosomal position Xq21.2-Xq21.3. These results confirm HDAC8 as a new member of the HDAC family.

show abstract

Section: Discussionmentioning

confidence: 99%

Cloning and characterization of a novel human histone deacetylase, HDAC8

Buggy

Sideris

Mak

et al. 2000

Biochemical Journal

155

101

View full text Add to dashboard Cite

show abstract

“…The Histone deacetylase 2 gene (HDAC2) was recently mapped to 6q21 (Betz et al, 1998) between D6S1563 and D6S1657, the CDR2 region. HDACs are considered tumour suppressor gene candidates as they may suppress transcription by modulating chromatin structure.…”

Section: Figurementioning

confidence: 99%

Multiple deleted regions on the long arm of chromosome 6 in astrocytic tumours

et al. 2000

View full text Add to dashboard Cite

Summary Chromosome 6 deletions are common in human neoplasms including gliomas. In order to study the frequency and identify commonly deleted regions of chromosome 6 in astrocytomas, 159 tumours (106 glioblastomas, 39 anaplastic astrocytomas and 14 astrocytomas malignancy grade II) were analysed using 31 microsatellite markers that span the chromosome. Ninety-five per cent of cases with allelic losses had losses affecting 6q. Allelic losses were infrequent in astrocytomas malignancy grade II (14%) but more usual in anaplastic astrocytomas (38%) and glioblastomas (37%). Evidence for clonal heterogeneity in the astrocytomas and anaplastic astrocytomas was frequently observed (i.e. co-existence of subpopulations with and without chromosome 6 deletions). Clonal heterogeneity was less common in glioblastomas. Five commonly deleted regions were identified on 6q. These observations suggest that a number of tumour suppressor genes are located on 6q and that these genes may be involved in the progression of astrocytic tumours.

show abstract

“…2642602]}, yeast ESA1 (16), and human CBP͞p300 (17), TAF II 250 (18), Tip60 (19), ACTR (20), and SRC-1 (21). In addition, the catalytic subunits of distinct histone deacetylase complexes shown to mediate transcriptional repression have been identified, including yeast and mammalian RPD3͞HDAC2 (22,23), yeast HDA1 and phd1 (24,25), maize HD1-A and HD2 (26)(27)(28), and human HDAC1 and HDAC3 (29)(30)(31).…”

mentioning

confidence: 99%

Crystal structure and mechanism of histone acetylation of the yeast GCN5 transcriptional coactivator

Trievel

Rojas

Sterner

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

177

152

View full text Add to dashboard Cite

The yeast GCN5 (yGCN5) transcriptional coactivator functions as a histone acetyltransferase (HAT) to promote transcriptional activation. Here, we present the high resolution crystal structure of the HAT domain of yGCN5 and probe the functional importance of a conserved glutamate residue. The structure reveals a central protein core associated with AcCoA binding that appears to be structurally conserved among a superfamily of N-acetyltransferases, including yeast histone acetyltransferase 1 and Serratia marcescens aminoglycoside 3-Nacetyltransferase. A pronounced cleft lying above this core, and flanked by N-and C-terminal regions that show no sequence conservation within N-acetyltransferase enzymes, is implicated by cross-species conservation and mutagenesis studies to be a site for histone substrate binding and catalysis. Located at the bottom of this cleft is a conserved glutamate residue (E173) that is in position to play an important catalytic role in histone acetylation. Functional analysis of an E173Q mutant yGCN5 protein implicates glutamate 173 to function as a general base for catalysis. Together, a correlation of the yGCN5 structure with functionally debilitating yGCN5 mutations provides a paradigm for understanding the structure͞function relationships of the growing number of transcriptional regulators that function as histone acetyltransferase enzymes.Gene activation is a tightly regulated process that relies on the coordinated activities of several different proteins. Sequencespecific transcriptional activators play an important role in nucleating gene expression by recruiting the basal transcriptional machinery, which includes TATA box-binding proteins, TAFs (TATA box-binding protein-associated proteins), polymerase, and other protein cofactors, to DNA (1, 2). Under physiological conditions, the transcriptional machinery has to deal with a DNA template that is complexed with histones that form nucleosomes and that are assembled into higher order chromatin (3). Because chromatin assembly strongly represses transcription (4, 5), DNA regulatory proteins must physically destabilize nucleosome͞DNA interactions to facilitate transcriptional activation.The relatively recent findings that histone acetyltransferase (HAT) and histone deacetyltransferase enzymes are proteins that had been previously characterized as transcriptional cofactors has revealed a direct mechanistic link between chromatin modification and transcriptional regulation (6-10). Specifically, a number of transcriptional cofactors with HAT activity have been identified, including GCN5 .Of the HAT enzymes identified to date, yGCN5 is currently the best characterized. Recombinant GCN5 has been shown to efficiently acetylate free histones with a strong preference for lysine 14 of histone H3 and a somewhat lower preference for lysines 8 and 16 of histone H4 (32). Interestingly, acetylation of nucleosomal histones requires that GCN5 be part of one of two distinct multiprotein complexes called Ada and SAGA (Spt-Ada-GCN5-acetyltransferase...

show abstract

Human Histone Deacetylase 2,HDAC2(HumanRPD3), Is Localized to 6q21 by Radiation Hybrid Mapping

Cited by 15 publications

References 5 publications

Cloning and characterization of a novel human histone deacetylase, HDAC8

Cloning and characterization of a novel human histone deacetylase, HDAC8

Multiple deleted regions on the long arm of chromosome 6 in astrocytic tumours

Crystal structure and mechanism of histone acetylation of the yeast GCN5 transcriptional coactivator

Contact Info

Product

Resources

About