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

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 and Anne Brunet ()
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Eric L. Greer: Stanford University, 300 Pasteur Drive, Stanford, California 94305, USA
Travis J. Maures: Stanford University, 300 Pasteur Drive, Stanford, California 94305, USA
Anna G. Hauswirth: Stanford University, 300 Pasteur Drive, Stanford, California 94305, USA
Erin M. Green: Stanford University, Stanford, California 94305, USA
Dena S. Leeman: Stanford University, 300 Pasteur Drive, Stanford, California 94305, USA
Géraldine S. Maro: Stanford University, Stanford, California 94305, USA
Shuo Han: Stanford University, 300 Pasteur Drive, Stanford, California 94305, USA
Max R. Banko: Stanford University, 300 Pasteur Drive, Stanford, California 94305, USA
Or Gozani: Cancer Biology Graduate Program, Stanford University, Stanford, California 94305, USA
Anne Brunet: Stanford University, 300 Pasteur Drive, Stanford, California 94305, USA

Nature, 2010, vol. 466, issue 7304, 383-387

Abstract: Methylation adds to lifespan Genes of the Sir2 family are known to influence longevity in yeast, in the worm Caenorhabditis elegans and in other organisms through an effect on histone deacetylation. This raises the question of whether other histone modifications also influence longevity. Greer et al. show that histone methylation regulates lifespan determination in C. elegans. Deficiencies in components of a conserved chromatin protein complex known as the ASH-2 complex, which trimethylates histone H3 at lysine 4 (H3K4), all extend worm lifespan. Conversely, the H3K4 demethylase RBR-2 is required for normal lifespan, consistent with the idea that an excess of H3K4 trimethylation shortens lifespan. This increase in longevity requires the presence of an intact adult germline and the continuous production of mature eggs, which suggests that the lifespan of the soma is regulated by an H3K4 methyltransferase/demethylase complex in the germline.

Date: 2010
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DOI: 10.1038/nature09195

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