Histone methylation and longevity

The process of ageing and longevity may be controlled biologically 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 pluri¬potency in mammals.
In this paper Greer et al identify the ASH-2 trithorax complex, which trirnethylates 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 normallifespan, consistent with the idea that an excess ofH3K 4 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 germ¬line 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 is regulated by an H3K4 methyltransferase/demethylase complex acting in the C. elegans germline.

Greer et al ( 2010 ) Members of the H3K4 trimethylation complex regulate llfespan in a germ line-dependent manner in C. elegans Nature vol 466 pp 383-387

Martin Eastwood
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