Publication Date:
2010-06-18
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3075006/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3075006/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Greer, Eric L -- Maures, Travis J -- Hauswirth, Anna G -- Green, Erin M -- Leeman, Dena S -- Maro, Geraldine S -- Han, Shuo -- Banko, Max R -- Gozani, Or -- Brunet, Anne -- AG31198/AG/NIA NIH HHS/ -- F31-AG032837/AG/NIA NIH HHS/ -- R01 AG031198/AG/NIA NIH HHS/ -- R01 AG031198-01A1/AG/NIA NIH HHS/ -- R01 AG031198-01A1S1/AG/NIA NIH HHS/ -- R01 AG031198-02/AG/NIA NIH HHS/ -- R01 AG031198-03/AG/NIA NIH HHS/ -- R01-AG31198/AG/NIA NIH HHS/ -- T32 CA009302/CA/NCI NIH HHS/ -- T32-CA009302/CA/NCI NIH HHS/ -- T32-HG000044/HG/NHGRI NIH HHS/ -- England -- Nature. 2010 Jul 15;466(7304):383-7. doi: 10.1038/nature09195. Epub 2010 Jun 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Stanford University, 300 Pasteur Drive, Stanford, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20555324" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Animals, Genetically Modified
;
Caenorhabditis elegans/enzymology/genetics/*physiology
;
Caenorhabditis elegans Proteins/genetics/*metabolism
;
Disorders of Sex Development
;
Epigenesis, Genetic
;
Gene Expression Regulation
;
Gene Knockdown Techniques
;
Germ Cells/cytology/*metabolism
;
Histone Demethylases/genetics/metabolism
;
Histone-Lysine N-Methyltransferase/genetics/metabolism
;
Histones/chemistry/*metabolism
;
Longevity/genetics/*physiology
;
Lysine/*metabolism
;
Male
;
Methylation
;
Multiprotein Complexes/chemistry/genetics/*metabolism
;
Nuclear Proteins/genetics/metabolism
;
RNA Interference
;
Retinoblastoma-Binding Protein 2/genetics/metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink
