費(fèi)城wistar研究所基因表達(dá)與調(diào)控研究項(xiàng)目組、生化項(xiàng)目組,、華盛頓大學(xué)病理學(xué)系等處的研究者在最新的Nature上發(fā)表細(xì)胞壽命研究的文章,，Histone H4 lysine 16 acetylation regulates cellular lifespan。
細(xì)胞在發(fā)育的過(guò)程中具有一個(gè)典型的特征：遺傳物質(zhì)不發(fā)生變化,，卻一直發(fā)生表觀遺傳學(xué)的改變,，甲基化和組蛋白修飾作用一直在改變細(xì)胞的發(fā)育。
Sirtuins是一類保守的NAD+依賴的脫乙?；?，具有通過(guò)各種途徑延長(zhǎng)有機(jī)體壽命的能力。然而,，關(guān)于sirtunis調(diào)節(jié)壽命的分子機(jī)制卻一直了解不多,。
本研究中,，Shelley L. Berger教授等人以酵母Sir2為研究對(duì)象,，解析它對(duì)細(xì)胞壽命的調(diào)節(jié)機(jī)制。
Sir2蛋白可去除細(xì)胞的H4賴氨酸 -16乙?；饔眠€可能誘導(dǎo)其他沉默蛋白的生成,。在老化的酵母細(xì)胞中，Sir2蛋白逐步減少,，并且伴隨H4賴氨酸 -16乙?；饔眉觿。糠謪^(qū)域的組蛋白消失,，這導(dǎo)致某些基因座的沉默機(jī)制停止,。
這些結(jié)果表明Sirtuins從演化角度來(lái)講其一個(gè)保守的功能，即通過(guò)使端粒染色質(zhì)保持不變,，來(lái)調(diào)控復(fù)制性衰老,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature 459, 802-807 (11 June 2009) | doi:10.1038/nature08085
Histone H4 lysine 16 acetylation regulates cellular lifespan
Weiwei Dang1, Kristan K. Steffen2, Rocco Perry1, Jean A. Dorsey1, F. Brad Johnson4, Ali Shilatifard5, Matt Kaeberlein3, Brian K. Kennedy2 & Shelley L. Berger1,6
1 Gene Expression and Regulation Program, The Wistar Institute Philadelphia, Pennsylvania 19104, USA
2 Department of Biochemistry,
3 Department of Pathology, University of Washington Seattle, Washington 98195, USA
4 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
5 Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA
6 Department of Cell & Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
7 Correspondence to: Shelley L. Berger1,6 Correspondence and requests for materials should be addressed to S.L.B.
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.
