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Transgenerational epigenetic inheritance of longevity in Caenorhabditis elegans

2011; Nature Portfolio; Volume: 479; Issue: 7373 Linguagem: Inglês

10.1038/nature10572

1476-4687

Eric Lieberman Greer, Travis J. Maures, Duygu Ucar, Anna G. Hauswirth, Elena Mancini, Jana P. Lim, Bérénice A. Benayoun, Yang Shi, Anne Brunet,

Intergenerational Family Dynamics and Caregiving

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. It is known that simple traits — flower characteristics in plants and eye colour in Drosophila, for instance — can be inherited in a transgenerational manner. This Article demonstrates the transgenerational epigenetic inheritance of a complex trait: acquired longevity in the roundworm Caenorhabditis elegans. The manipulation of H3K4me3 chromatin modifiers of the ASH-2 complex in the parental generation extends the lifespan of the descendents for three subsequent generations. These findings imply that chromatin changes in parents might not be entirely reset between generations, and provide the first evidence for epigenetic inheritance of lifespan. The H3K4me3 regulatory complex is conserved in mammals, but more work is needed to determine whether manipulations of the complex have a heritable effect on longevity in mammals.