Transgenerational epigenetic inheritance of longevity in Caenorhabditis elegans.
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.
Department of Genetics, Stanford University, 300 Pasteur Drive, Stanford, California 94305, USA.
Eric L
EL
Greer
Travis J
TJ
Maures
Duygu
D
Ucar
Anna G
AG
Hauswirth
Elena
E
Mancini
Jana P
JP
Lim
Bérénice A
BA
Benayoun
Yang
Y
Shi
Anne
A
Brunet
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D044127:Epigenesis, Genetic / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D056466:Histone Demethylases / Q000235:genetics / Q000378:metabolism; D011495:Histone-Lysine N-Methyltransferase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D006657:Histones; D040582:Inheritance Patterns; D008136:Longevity / Q000235:genetics* / Q000502:physiology; D008297:Male; D008745:Methylation; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010375:Pedigree; D056485:Retinoblastoma-Binding Protein 2 / Q000235:genetics / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D002843:Chromatin; D006657:Histones; D009687:Nuclear Proteins; C449640:SET-2 protein, C elegans; C569241:wdr-5.1 protein, C elegans; D056466:Histone Demethylases; C519283:RBR-2 protein, C elegans; D056485:Retinoblastoma-Binding Protein 2; C551693:ASH-2 protein, C elegans; D011495:Histone-Lysine N-Methyltransferase