Nature：甲基化可以延长寿命（附原文）

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% x$ i$ a( J: P4 O: lSir2家族的基因已知通过对组蛋白脱乙酰作用的一个效应来影响酵母、线虫和其他生物的寿命。这便提出一个问题：其他组蛋白修饰是否也影响寿命？Greer等人发现，组蛋白甲基化调控线虫的寿命。被称为“ASH-2复合物”的一个保守的染色质蛋白复合物（该复合物在赖氨酸-4(H3K4)处使组蛋白H3发生“三甲基化”）的构成成分的缺失都会延长线虫寿命。: k5 b; G* @$ |9 V" ~6 F

5 }  X/ j* ~' v( ?" @  ~; `7 }' ^相反，H3K4脱甲基酶rbr-2是维持正常寿命所必需的，这与认为过多的H3K4“三甲基化”缩短寿命的观点是一致的。这种寿命延长要求一个完好的成年生殖细胞系的存在以及成熟卵的持续产生，这说明体细胞的寿命是由生殖细胞中一个H3K4甲基转移酶/脱甲基酶复合物调控的。
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1 d4 l5 a  Z* o+ N. J  t# bNature doi:10.1038/nature091957 w' _% s; q) ^+ w- n5 E" K

' h$ R$ ]6 d0 r% w0 k$ T3 I2 WMembers of the H3K4 trimethylation complex regulate lifespan in a germline-dependent manner in C. elegans  [& ]1 I* ?& K2 D0 B- ?7 H
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 Brunet0 H8 N: r* e" ^

8 S8 `6 G& {# L0 p* i( ?: |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.
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4楼原文 感谢shuc.chen提供

yuguangju99

谢谢

huns1107

多谢楼主分享！

shuc.chen

甲基化还包括DNA水平的甲基化，它和组蛋白的甲基化一样，都是抑制或促进了某一基因的表达，那问题是DNA的甲基化是否也和寿命的长短相关呢？不管是组蛋白，还是DNA，甚至还有更多的修饰形式（如磷酸化，泛素化……），其本质我认为还是某一基因系列（与寿命长短有关）转录水平的调节，另外弄清楚相应的细胞信号通络同样重要，看了下摘要，好像说的还不够细致啊

shuc.chen

附上原文，供大家研究

sniper

回复 1# initiation 1 G' J! \. c, u( X/ H2 Y: x
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