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首页> 外文期刊>Nature >Histone H4 lysine 16 acetylation regulates cellular lifespan
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Histone H4 lysine 16 acetylation regulates cellular lifespan

机译：组蛋白H4赖氨酸16乙酰化调节细胞寿命

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摘要

Cells undergoing developmental processes are characterized by persistent non-genetic alterations in chromatin, termed epigenetic changes, represented by distinct patterns of DNA methylation and histone post-translational modifications. Sirtuins, a group of conserved NAD~+-dependent deacetylases or ADP-ribosyltransferases, promote longevity in diverse organisms; however, their molecular mechanisms in ageing regulation remain poorly understood. Yeast Sir2, the first member of the family to be found, establishes and maintains chromatin silencing by removing histone H4 lysine 16 acetylation and bringing in other silencing proteins. Here we report an age-associated decrease in Sir2 protein abundance accompanied by an increase in H4 lysine 16 acetylation and loss of histones at specific subtelomeric regions in replicatively old yeast cells, which results in compromised transcriptional silencing at these loci. Antagonizing activities of Sir2 and Sas2, a histone acetyltransferase, regulate the replicative lifespan through histone H4 lysine 16 at subtelomeric regions. This pathway, distinct from existing ageing models for yeast, may represent an evolutionarily conserved function of sirtuins in regulation of replicative ageing by maintenance of intact telomeric chromatin.
机译：经历发育过程的细胞的特征在于染色质的持续非遗传改变，称为表观遗传改变，以DNA甲基化和组蛋白翻译后修饰的不同模式表示。 Sirtuins是一组保守的NAD〜+依赖性脱乙酰基酶或ADP-核糖基转移酶，可促进多种生物的寿命。然而，它们在衰老调节中的分子机制仍然知之甚少。酵母Sir2是该家族的第一个成员，它通过去除组蛋白H4赖氨酸16乙酰化并引入其他沉默蛋白来建立和维持染色质沉默。在这里，我们报告了与年龄相关的Sir2蛋白丰度的下降，伴随着H4赖氨酸16乙酰化的增加以及在可复制的旧酵母细胞中特定亚端粒区域的组蛋白的丢失，这导致这些基因座的转录沉默受到损害。 Sir2和Sas2（一种组蛋白乙酰基转移酶）的拮抗活性通过亚端粒区域的组蛋白H4赖氨酸16调节复制寿命。该途径不同于现有的酵母老化模型，可能代表沉默调节蛋白在通过维持完整的端粒染色质来调节复制性老化中的进化保守功能。

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  • 来源
    《Nature》 |2009年第7248期|802-807|共6页
  • 作者

    Weiwei Dang; Kristan K. Steffen; Rocco Perry; Jean A. Dorsey; F. Brad Johnson; Ali Shilatifard; Matt Kaeberlein; Brian K. Kennedy; Shelley L. Berger;

  • 作者单位

    Gene Expression and Regulation Program, The Wistar Institute Philadelphia, Pennsylvania 19104, USA;

    Department of Biochemistry, University of Washington Seattle, Washington 98195, USA;

    Gene Expression and Regulation Program, The Wistar Institute Philadelphia, Pennsylvania 19104, USA;

    Gene Expression and Regulation Program, The Wistar Institute Philadelphia, Pennsylvania 19104, USA;

    Department of Pathology and Laboratory Medicine, Cell and Molecular Biology Group, Biomedical Graduate Studies and Institute on Aging, University of Pennsylvania School of Medicine, Philadelphia 19104, Pennsylvania, USA;

    Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA;

    Department of Pathology, University of Washington Seattle, Washington 98195, USA;

    Department of Biochemistry, University of Washington Seattle, Washington 98195, USA;

    Gene Expression and Regulation Program, The Wistar Institute Philadelphia, Pennsylvania 19104, USA Department of Cell & Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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