Transgenerational epigenetic inheritance of longevity in Caenorhabditis elegans

被引:437
作者
Greer, Eric L. [1 ,2 ,3 ]
Maures, Travis J. [1 ]
Ucar, Duygu [1 ]
Hauswirth, Anna G. [1 ]
Mancini, Elena [1 ]
Lim, Jana P. [1 ]
Benayoun, Berenice A. [1 ]
Shi, Yang [2 ,3 ]
Brunet, Anne [1 ]
机构
[1] Stanford Univ, Dept Genet, Stanford, CA 94305 USA
[2] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA
[3] Childrens Hosp, Div Newborn Med, Boston, MA 02115 USA
关键词
SYSTEMATIC RNAI SCREEN; LIFE-SPAN; C; ELEGANS; H3K4; TRIMETHYLATION; STRESS RESISTANCE; GENES; COMPLEX; METHYLATION; DEMETHYLATION; CHROMATIN;
D O I
10.1038/nature10572
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Chromatin modifiers regulate lifespan in several organisms, raising the question of whether changes in chromatin states in the parental generation could be incompletely reprogrammed in the next generation and thereby affect the lifespan of descendants. The histone H3 lysine 4 trimethylation (H3K4me3) complex, composed of ASH-2, WDR-5 and the histone methyltransferase SET-2, regulates Caenorhabditis elegans lifespan. Here we show that deficiencies in the H3K4me3 chromatin modifiers ASH-2, WDR-5 or SET-2 in the parental generation extend the lifespan of descendants up until the third generation. The transgenerational inheritance of lifespan extension by members of the ASH-2 complex is dependent on the H3K4me3 demethylase RBR-2, and requires the presence of a functioning germline in the descendants. Transgenerational inheritance of lifespan is specific for the H3K4me3 methylation complex and is associated with epigenetic changes in gene expression. Thus, manipulation of specific chromatin modifiers only in parents can induce an epigenetic memory of longevity in descendants.
引用
收藏
页码:365 / U204
页数:9
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