Deactivation of the GATA Transcription Factor ELT-2 Is a Major Driver of Normal Aging in C. elegans

被引：36

作者：

Mann, Frederick G. ^{[1
,2
]}

Van Nostrand, Eric L. ^{[3
]}

Friedland, Ari E. ^{[4
]}

Liu, Xiao ^{[5
]}

Kim, Stuart K. ^{[1
,2
]}

机构：

[1] Stanford Univ, Med Ctr, Dept Genet, Stanford, CA 94305 USA

[2] Stanford Univ, Med Ctr, Dept Dev Biol, Stanford, CA 94305 USA

[3] Univ Calif San Diego, Inst Genom Med, Dept Cellular & Mol Med, La Jolla, CA 92093 USA

[4] Editas Med, Cambridge, MA USA

[5] Tsinghua Univ, Sch Life Sci, Beijing 100084, Peoples R China

来源：

PLOS GENETICS | 2016年 / 12卷 / 04期

关键词：

CAENORHABDITIS-ELEGANS; INTEGRATIVE ANALYSIS; EXPRESSION PROFILES; GENE-EXPRESSION; CELL FATE; LONGEVITY; BACTERIAL; INTESTINE; GENOME; RESTRICTION;

D O I：

10.1371/journal.pgen.1005956

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

To understand the molecular processes underlying aging, we screened modENCODE ChIP-seq data to identify transcription factors that bind to age-regulated genes in C. elegans. The most significant hit was the GATA transcription factor encoded by elt-2, which is responsible for inducing expression of intestinal genes during embryogenesis. Expression of ELT-2 decreases during aging, beginning in middle age. We identified genes regulated by ELT-2 in the intestine during embryogenesis, and then showed that these developmental genes markedly decrease in expression as worms grow old. Overexpression of elt-2 extends lifespan and slows the rate of gene expression changes that occur during normal aging. Thus, our results identify the developmental regulator ELT-2 as a major driver of normal aging in C. elegans.

引用

页数：26

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