Characterization of a bidirectional promoter shared between two human genes related to aging:: SIRT3 and PSMD13
Characterization of a bidirectional promoter shared between two human genes related to aging:: SIRT3 and PSMD13
复制标题
DOI：
10.1016/j.ygeno.2006.09.004
复制
发表时间：
2007-01-01
期刊：
影响因子：
4.4
通讯作者：
De Benedictis, G.
中科院分区：
文献类型：
--
作者：
Bellizzi, D.;Dato, S.;De Benedictis, G.
人类SIRT3基因含有一个内含子VNTR增强子，其变异性与寿命相关。SIRT3 5'侧区包含编码26S蛋白酶体p40.5调控亚基的PSMD13基因。蛋白酶体是一种多催化的蛋白酶，其功能随着年龄的增长而下降。SIRT3和PSMD13。以头对头的结构连接（788-bp的基因间区）。两个基因的分子结构都与衰老有关，这促使我们在它们之间寻找共同的调节机制。PSMD13-SIRT3基因间区缺失突变体转染HeLa细胞的实验显示，PSMD13-SIRT3基因间区缺失突变体具有双向协同调控的复杂途径。此外，对710名受试者（18-108岁）进行了连锁不平衡（LD）分析，筛选了A2163IG （PSMD13的标记）、G477T和VNTRintron5 （SIRT3的标记），结果显示LD较高，百岁老人和年轻人的PSMD13-SIRT3单倍型池存在显著差异。(c) 2006爱思唯尔公司版权所有。
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 A2163IG (markerof PSMD13), and for G477T and VNTRintron5 (markers of SIRT3), revealed high LD, with significantly different PSMD13-SIRT3 haplotype pools between samples of centenarians and younger people. (c) 2006 Elsevier Inc. All rights reserved.