Sumoylation at chromatin governs coordinated repression of a transcriptional program essential for cell growth and proliferation.
Sumoylation at chromatin governs coordinated repression of a transcriptional program essential for cell growth and proliferation.
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DOI：
10.1101/gr.154872.113
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发表时间：
2013-10
期刊：
影响因子：
7
通讯作者：
Dejean A
中科院分区：
文献类型：
--
作者：
Neyret-Kahn H;Benhamed M;Ye T;Le Gras S;Cossec JC;Lapaquette P;Bischof O;Ouspenskaia M;Dasso M;Seeler J;Davidson I;Dejean A
尽管有许多关于特异性SUMO化转录调控因子的研究，但SUMO在染色质上与转录调控相关的整体作用仍然很大程度上未知。在这里，我们确定了SUMO 1和SUMO 2/3，以及UBC 9（由UBE 2 I编码）和PIASY（由PIAS 4编码）的全基因组定位，这两个标记物是活跃的类小泛素化，沿着Pol II和组蛋白标记物在增殖与衰老的人成纤维细胞中以及基因表达谱。我们发现，而SUMO单独广泛分布在基因组中，在活性启动子处具有强关联，活性SUMO化最显著地发生在组蛋白和蛋白质生物发生基因的启动子处，以及Pol I rRNA和Pol III tRNA。值得注意的是，这四类基因通过抑制SUMO化而上调，表明SUMO通常起抑制它们表达的作用。与这一发现相一致的是，小泛素化缺陷细胞显示出细胞大小和整体蛋白水平的增加。引人注目的是，我们发现在衰老细胞中，SUMO机制选择性地保留在组蛋白和tRNA基因簇中，而它从所有其他独特的染色质区域大量释放。这些数据，揭示了相扑景观的高度动态的性质，表明在组蛋白和tRNA基因座的抑制环境的维护是衰老状态的标志。因此，在我们的研究中采取的方法允许识别一个共同的生物输出，并发现了迄今未知的功能，在染色质上的活性sumoylation作为一个关键机制，在动态标记染色质的一个简单的修饰剂，协调一致的转录调控的网络的基因细胞生长和增殖。
Despite numerous studies on specific sumoylated transcriptional regulators, the global role of SUMO on chromatin in relation to transcription regulation remains largely unknown. Here, we determined the genome-wide localization of SUMO1 and SUMO2/3, as well as of UBC9 (encoded by UBE2I) and PIASY (encoded by PIAS4), two markers for active sumoylation, along with Pol II and histone marks in proliferating versus senescent human fibroblasts together with gene expression profiling. We found that, whereas SUMO alone is widely distributed over the genome with strong association at active promoters, active sumoylation occurs most prominently at promoters of histone and protein biogenesis genes, as well as Pol I rRNAs and Pol III tRNAs. Remarkably, these four classes of genes are up-regulated by inhibition of sumoylation, indicating that SUMO normally acts to restrain their expression. In line with this finding, sumoylation-deficient cells show an increase in both cell size and global protein levels. Strikingly, we found that in senescent cells, the SUMO machinery is selectively retained at histone and tRNA gene clusters, whereas it is massively released from all other unique chromatin regions. These data, which reveal the highly dynamic nature of the SUMO landscape, suggest that maintenance of a repressive environment at histone and tRNA loci is a hallmark of the senescent state. The approach taken in our study thus permitted the identification of a common biological output and uncovered hitherto unknown functions for active sumoylation at chromatin as a key mechanism that, in dynamically marking chromatin by a simple modifier, orchestrates concerted transcriptional regulation of a network of genes essential for cell growth and proliferation.
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影响因子：
7.8
作者：
Azuma, Yoshiaki;Arnaoutov, Alexei;Dasso, Mary
通讯作者：
Dasso, Mary
影响因子：
16
作者：
Chandra, Tamir;Kirschner, Kristina;Thuret, Jean-Yves;Pope, Benjamin D.;Ryba, Tyrone;Newman, Scott;Ahmed, Kashif;Samarajiwa, Shamith A.;Salama, Rafik;Carroll, Thomas;Stark, Rory;Janky, Rekin's;Narita, Masako;Xue, Lixiang;Chicas, Agustin;Nunez, Sabrina;Janknecht, Ralf;Hayashi-Takanaka, Yoko;Wilson, Michael D.;Marshall, Aileen;Odom, Duncan T.;Babu, M. Madan;Bazett-Jones, David P.;Tavare, Simon;Edwards, Paul A. W.;Lowe, Scott W.;Kimura, Hiroshi;Gilbert, David M.;Narita, Masashi
通讯作者：
Narita, Masashi
影响因子：
16.8
作者：
Mahajan K;Fang B;Koomen JM;Mahajan NP
通讯作者：
Mahajan NP
影响因子：
5.3
作者：
MacPherson, Melissa J.;Beatty, Linda G.;Sadowski, Paul D.
通讯作者：
Sadowski, Paul D.
影响因子：
14.9
作者：
Flicek P;Ahmed I;Amode MR;Barrell D;Beal K;Brent S;Carvalho-Silva D;Clapham P;Coates G;Fairley S;Fitzgerald S;Gil L;García-Girón C;Gordon L;Hourlier T;Hunt S;Juettemann T;Kähäri AK;Keenan S;Komorowska M;Kulesha E;Longden I;Maurel T;McLaren WM;Muffato M;Nag R;Overduin B;Pignatelli M;Pritchard B;Pritchard E;Riat HS;Ritchie GR;Ruffier M;Schuster M;Sheppard D;Sobral D;Taylor K;Thormann A;Trevanion S;White S;Wilder SP;Aken BL;Birney E;Cunningham F;Dunham I;Harrow J;Herrero J;Hubbard TJ;Johnson N;Kinsella R;Parker A;Spudich G;Yates A;Zadissa A;Searle SM
通讯作者：
Searle SM