Chromosomal organization and localization of the human histone deacetylase 9 gene (HDAC9).
Epigenetically mediated modulation of gene promoter function through histone acetylation modifying enzymes, which regulate the acetylation state of histone proteins and other promoter-bound transcription factors, is increasingly appreciated as a key component in the regulation of reversible gene expression. While histone acetyltransferases (HATs), which are frequently part of multisubunit coactivator complexes, lead to the relaxation of chromatin structure and transcriptional activation, histone deacetylases (HDACs) tend to associate with multisubunit corepressor complexes, which result in chromatin condensation and transcriptional repression of specific target genes. We have isolated and characterized the human HDAC9 genomic sequence, which spans a region of 458 kb and which has one single chromosomal locus. Determination of the exon-intron splice-junctions established that HDAC9 is encoded by 23 exons ranging in size from 22 bp (exon 1) to 264 bp (exon 11). Characterization of the 5' flanking genomic region revealed that the human HDAC9 promoter lacks both the canonical TATA and CCAAT boxes; CpG elements are missing. The human HDAC9 open reading frame is 3036 bp long and encodes a 1011 aa protein with a predictive molecular weight of 111.3 kDa and an isoelectric point of 6.41. Fluorescence in situ hybridization analysis localized the human HDAC9 gene to chromosome 7p21, a region which has been associated particularly with the pathogenesis of gynecological tumors.
Mahlknecht
Ulrich
U
University of Frankfurt Medical Center, Department of Hematology/Oncology, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany. Mahlknecht@em.uni-frankfurt.de
Schnittger
Susanne
S
Will
Jutta
J
Cicek
Nurten
N
Hoelzer
Dieter
D
D000595:Amino Acid Sequence; D001483:Base Sequence; D002874:Chromosome Mapping; D002897:Chromosomes, Human, Pair 7; D017931:DNA Primers; D018076:DNA, Complementary / Q000235:genetics; D005819:Genetic Markers; D006655:Histone Deacetylases / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D012097:Repressor Proteins / Q000235:genetics*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D017931:DNA Primers; D018076:DNA, Complementary; D005819:Genetic Markers; D012097:Repressor Proteins; D006655:Histone Deacetylases