Cloning, chromosomal characterization and mapping of the NAD-dependent histone deacetylases gene sirtuin 1.
Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase, which belongs to the silent information regulator 2 (Sir2) family of sirtuin histone deacetylases (HDACs). The yeast Sir2 protein and its mammalian derivatives play a central role in epigenetic gene silencing, DNA repair and recombination, cell-cycle, microtubule organization, and in the regulation of aging. We have isolated and characterized the human Sirt1 genomic sequence, which spans a region of 33,660 bp and which has one single genomic locus. Determination of the exon-intron splice junctions established that SIRT1 is encoded by 9 exons ranging in size from 80 bp (exon 6) to 2,120 bp (exon 9). Characterization of the 5' flanking genomic region, which precedes the Sirt1 open reading frame, revealed a CCAAT-box and a number of NF-kappaB and GATA transcription factor binding sites in addition to a small 350 bp CpG island. The 4,107 bp human Sirt1 mRNA has an open reading frame of 2,244 bp and encodes a 747 aa protein with a predictive molecular weight of 81.7 kDa and an isoelectric point of 4.55. Fluorescence in situ hybridization analysis localized the human Sirt1 gene to chromosome 10q21.3.
Voelter-Mahlknecht
Susanne
S
Department of Occupational, Social and Environmental Medicine, University of Mainz, D-55131 Mainz, Germany.
Mahlknecht
Ulrich
U
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10; D003001:Cloning, Molecular; D005091:Exons; D006655:Histone Deacetylases / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D010802:Phylogeny; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D056564:Sirtuin 1; D037761:Sirtuins / Q000145:classification / Q000235:genetics* / Q000378:metabolism
C447939:SIRT1 protein, human; D056564:Sirtuin 1; D037761:Sirtuins; D006655:Histone Deacetylases