Characterization of a bidirectional promoter shared between two human genes related to aging: SIRT3 and PSMD13.
The human SIRT3 gene contains an intronic VNTR enhancer whose variability is correlated with life span. The SIRT3 5' flanking region encompasses the PSMD13 gene encoding the p40.5 regulator subunit of the 26S proteasome. Proteasome is a multicatalytic proteinase whose function declines with aging. SIRT3 and PSMD13 are linked in a head-to-head configuration (788-bp intergenic region). The molecular configuration of two genes that are both related to aging prompted us to search for shared regulatory mechanisms between them. Transfection experiments carried out in HeLa cells by deletion mutants of the PSMD13-SIRT3 intergenic region showed a complex pathway of coregulation acting in both directions. Furthermore, linkage disequilibrium (LD) analyses carried out in a sample of 710 subjects (18-108 years of age) screened for A21631G (marker of PSMD13), and for G477T and VNTR(intron5) (markers of SIRT3), revealed high LD, with significantly different PSMD13-SIRT3 haplotype pools between samples of centenarians and younger people.
Bellizzi
D
D
Department of Cell Biology, University of Calabria, 87030 Rende, Italy.
Dato
S
S
Cavalcante
P
P
Covello
G
G
Di Cianni
F
F
Passarino
G
G
Rose
G
G
De Benedictis
G
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D001483:Base Sequence; D002874:Chromosome Mapping; D004247:DNA / Q000235:genetics; D021901:DNA, Intergenic; D005260:Female; D017930:Genes, Reporter; D005828:Genetics, Population; D006239:Haplotypes; D006367:HeLa Cells; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats; D024101:Mitochondrial Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D046988:Proteasome Endopeptidase Complex / Q000235:genetics*; D017384:Sequence Deletion; D056566:Sirtuin 3; D037761:Sirtuins / Q000235:genetics*
D021901:DNA, Intergenic; D024101:Mitochondrial Proteins; D004247:DNA; D046988:Proteasome Endopeptidase Complex; C466093:SIRT3 protein, human; D056566:Sirtuin 3; D037761:Sirtuins; C119011:26S proteasome non-ATPase regulatory subunit 13