Members of the H3K4 trimethylation complex regulate lifespan in a germline-dependent manner in C. elegans View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2010-07

AUTHORS

Eric L. Greer, Travis J. Maures, Anna G. Hauswirth, Erin M. Green, Dena S. Leeman, Géraldine S. Maro, Shuo Han, Max R. Banko, Or Gozani, Anne Brunet

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. More... »

PAGES

383

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nature09195

DOI

http://dx.doi.org/10.1038/nature09195

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1036229096

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/20555324


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