The methyltransferase Suv39h1 links the SUMO pathway to HP1α marking at pericentric heterochromatin

The methyltransferase Suv39h1 links the SUMO pathway to HP1α marking at pericentric heterochromatin
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DOI:
10.1038/ncomms12224
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发表时间:
2016-07
影响因子:
16.6
通讯作者:
C. Maison;Delphine Bailly;J. Quivy;G. Almouzni
C. Maison;Delphine Bailly;J. Quivy;G. Almouzni
中科院分区:
综合性期刊1区
文献类型:
--
作者:
C. Maison;Delphine Bailly;J. Quivy;G. Almouzni

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组蛋白H3在赖氨酸9上的三甲基化(H3 K9 me 3)--由HP 1识别的依赖于Suv 39 h赖氨酸甲基转移酶(KMT)的标记--为读者/作者模型解释HP 1在哺乳动物中的臂间异染色质积累提供了基础。在此,我们鉴定了Suv 39 h1蛋白,作为体外和体内HP 1 α类小泛素化的独特增强剂。负责促进HP 1 α类小泛素化的区域(aa 1 -167)与KMT催化结构域不同,并介导与Ubc 9的结合。将Suv 39 h 1的1-167结构域连接到臂间异染色质上,而不是不能结合Ubc 9的突变体,加速了HP 1 α对这些结构域的新靶向。我们的研究结果建立了一个意想不到的功能Suv 39 h1,不同的KMT活动,异染色质形成的主要作用。我们将讨论如何将Suv 39 h1与SUMO通路联系起来,为我们对核结构域组织和生理功能的一般看法提供概念上的影响。
The trimethylation of histone H3 on lysine 9 (H3K9me3) – a mark recognized by HP1 that depends on the Suv39h lysine methyltransferases (KMTs) – has provided a basis for the reader/writer model to explain HP1 accumulation at pericentric heterochromatin in mammals. Here, we identify the Suv39h1 paralog, as a unique enhancer of HP1α sumoylation bothin vitroandin vivo. The region responsible for promoting HP1α sumoylation (aa1–167) is distinct from the KMT catalytic domain and mediates binding to Ubc9. Tethering the 1–167 domain of Suv39h1 to pericentric heterochromatin, but not mutants unable to bind Ubc9, accelerates thede novotargeting of HP1α to these domains. Our results establish an unexpected feature of Suv39h1, distinct from the KMT activity, with a major role for heterochromatin formation. We discuss how linking Suv39h1 to the SUMO pathway provides conceptual implications for our general view on nuclear domain organization and physiological functions.