Sir2家族的基因已知通過(guò)對(duì)組蛋白脫乙酰作用的一個(gè)效應(yīng)來(lái)影響酵母,、線蟲(chóng)和其他生物的壽命。這便提出一個(gè)問(wèn)題：其他組蛋白修飾是否也影響壽命,？Greer等人發(fā)現(xiàn),，組蛋白甲基化調(diào)控線蟲(chóng)的壽命。被稱(chēng)為“ASH-2復(fù)合物”的一個(gè)保守的染色質(zhì)蛋白復(fù)合物（該復(fù)合物在賴(lài)氨酸-4(H3K4)處使組蛋白H3發(fā)生“三甲基化”）的構(gòu)成成分的缺失都會(huì)延長(zhǎng)線蟲(chóng)壽命,。
相反,，H3K4脫甲基酶rbr-2是維持正常壽命所必需的，這與認(rèn)為過(guò)多的H3K4“三甲基化”縮短壽命的觀點(diǎn)是一致的,。這種壽命延長(zhǎng)要求一個(gè)完好的成年生殖細(xì)胞系的存在以及成熟卵的持續(xù)產(chǎn)生,，這說(shuō)明體細(xì)胞的壽命是由生殖細(xì)胞中一個(gè)H3K4甲基轉(zhuǎn)移酶/脫甲基酶復(fù)合物調(diào)控的。(生物谷Bioon.net)
生物谷推薦原文出處：
Nature doi:10.1038/nature09195
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& Anne Brunet
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 family1, 2, 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 mammals3. Regulators of histone methylation have been associated with ageing in worms4, 5, 6, 7 and flies8, but characterization of their role and mechanism of action has been limited. Here we identify the ASH-2 trithorax complex9, 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.
