韩国科学发现抑癌基因--医学相关新知

抑癌基因

September 16, 2005: 19 (6)
"Sumoylation and Heterochromatin"
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SUMO Modification Is Involved in the Maintenance of Heterochromatin Stability in Fission Yeast

Jin A Shin,^¹,⁴Eun Shik Choi,^¹,⁴Hyun Soo Kim,^¹Jenny C.Y. Ho,^²,⁵Felicity Z. Watts,2 Sang Dai Park,3 and Yeun Kyu Jang1,*
　

Several studies have suggested that SUMO may participate in the regulation of heterochromatin, but direct evidence is lacking. Here, we present a direct link between sumoylation and heterochromatin stability. SUMO deletion impaired silencing at heterochromatic regions and induced histone H3 Lys4 methylation, a hallmark of active chromatin in fission yeast.

Our findings showed that the SUMO-conjugating enzyme Hus5/Ubc9 interacted with the conserved heterochromatin proteins Swi6, Chp2 (a paralog of Swi6), and Clr4 (H3 Lys9 methyltransferase). Moreover, chromatin immunoprecipitation (ChIP) revealed that Hus5 was highly enriched in heterochromatic regions in a heterochromatin-dependent manner, suggesting a direct role of Hus5 in heterochromatin formation. We also found that Swi6, Chp2, and Clr4 themselves can be sumoylated in vivo and defective sumoylation of Swi6 or Chp2 compromised silencing.

These results indicate that Hus5 associates with heterochromatin through interactions with heterochromatin proteins and modifies substrates whose sumoylations are required for heterochromatin stability, including heterochromatin proteins themselves.

Volume 19, Issue 6 , 16 September 2005, Pages 817-828

heterochromatin ：

Tightly coiled chromosomal material that stains deeply during interphase and is believed to be genetically inactive.

异染色质：紧紧盘绕在一起的染色体物质，在分裂期间染色，据信在基因中并不活跃

Heterochromatin

（异染色质）

一些研究提示：SUMO可以参与调节heterochromatin[异染色质]，但缺乏直接的证据。我们在里提供一个直接的例证，sumo物质与异染色质有直接关联。（韩国国家癌症中心致癌基因研究小组）

去除SUMO削弱了其对异染质片断的抑制，诱发 histone H3 Lys4，后者是在裂殖酵母中核物质活跃的特征。

     发现：SUMO相关酶Hus5/Ubc9与保存的异染色质蛋白Swi6, Chp2 , Clr4相结合。

    这些结果表明：Hus5 配合异染色质通过与异染色质蛋白来修正作用底物SUMO物质来维持异染色质的稳定性，包括异染色质蛋白自身。

以上说法比较晦涩，JERRYDOCTOR一句话解释：

细胞内SUMO基因的缺失会引起一种染色体的组成成分即异染色质的高度不稳定。and 人们知道，染色体不稳定是地会引发癌症。

以上的研究结果作为《分子细胞》的一期封面文章发表于16 September 2005。