RRC ID 46598
Author Greer EL, Maures TJ, Hauswirth AG, Green EM, Leeman DS, Maro GS, Han S, Banko MR, Gozani O, Brunet A.
Title Members of the H3K4 trimethylation complex regulate lifespan in a germline-dependent manner in C. elegans.
Journal Nature
Abstract The plasticity of ageing suggests that longevity may be controlled epigenetically by specific alterations in chromatin state. The link between chromatin and ageing has mostly focused on histone deacetylation by the Sir2 family, but less is known about the role of other histone modifications in longevity. Histone methylation has a crucial role in development and in maintaining stem cell pluripotency in mammals. Regulators of histone methylation have been associated with ageing in worms and flies, but characterization of their role and mechanism of action has been limited. Here we identify the ASH-2 trithorax complex, which trimethylates histone H3 at lysine 4 (H3K4), as a regulator of lifespan in Caenorhabditis elegans in a directed RNA interference (RNAi) screen in fertile worms. Deficiencies in members of the ASH-2 complex-ASH-2 itself, WDR-5 and the H3K4 methyltransferase SET-2-extend worm lifespan. Conversely, the H3K4 demethylase RBR-2 is required for normal lifespan, consistent with the idea that an excess of H3K4 trimethylation-a mark associated with active chromatin-is detrimental for longevity. Lifespan extension induced by ASH-2 complex deficiency requires the presence of an intact adult germline and the continuous production of mature eggs. ASH-2 and RBR-2 act in the germline, at least in part, to regulate lifespan and to control a set of genes involved in lifespan determination. These results indicate that the longevity of the soma is regulated by an H3K4 methyltransferase/demethylase complex acting in the C. elegans germline.
Volume 466(7304)
Pages 383-7
Published 2010-7-15
DOI 10.1038/nature09195
PII nature09195
PMID 20555324
PMC PMC3075006
MeSH Animals Animals, Genetically Modified Caenorhabditis elegans / enzymology Caenorhabditis elegans / genetics Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Disorders of Sex Development Epigenesis, Genetic Gene Expression Regulation Gene Knockdown Techniques Germ Cells / cytology Germ Cells / metabolism* Histone Demethylases / genetics Histone Demethylases / metabolism Histone-Lysine N-Methyltransferase / genetics Histone-Lysine N-Methyltransferase / metabolism Histones / chemistry Histones / metabolism* Longevity / genetics Longevity / physiology* Lysine / metabolism* Male Methylation Multiprotein Complexes / chemistry Multiprotein Complexes / genetics Multiprotein Complexes / metabolism* Nuclear Proteins / genetics Nuclear Proteins / metabolism RNA Interference Retinoblastoma-Binding Protein 2 / genetics Retinoblastoma-Binding Protein 2 / metabolism
IF 42.779
Times Cited 271
C.elegans tm1231