Kadoch Cigall, Copeland Robert A, Keilhack Heike
Dana-Farber Cancer Institute and Harvard Medical School , 450 Brookline Avenue, Boston, Massachusetts 02215, United States.
Epizyme Inc. , 400 Technology Square, 4th floor, Cambridge, Massachusetts 02139, United States.
Biochemistry. 2016 Mar 22;55(11):1600-14. doi: 10.1021/acs.biochem.5b01191. Epub 2016 Feb 17.
The dynamic structure of histones and DNA, also known as chromatin, is regulated by two classes of enzymes: those that mediate covalent modifications on either histone proteins or DNA and those that use the energy generated by ATP hydrolysis to mechanically alter chromatic structure. Both classes of enzymes are often found in large protein complexes. In this review, we describe two such complexes: polycomb repressive complex 2 (PRC2), with the protein methyltransferase EZH2 as its catalytic subunit, and the ATP-dependent chromatin remodeler switch/sucrose non-fermentable (SWI/SNF). EZH2 catalyzes the methylation of lysine 27 on histone H3, a covalent chromatin modification that is associated with repressed heterochromatin. The catalytic activity of SWI/SNF, in contrast, leads to a state of open chromatin associated with active transcription. In this review, we discuss the biochemical properties of both complexes, outline the principles of their regulation, and describe their opposing roles in normal development, which can be perturbed in disease settings such as cancer.
组蛋白和DNA的动态结构，也称为染色质，由两类酶调控：一类是介导组蛋白或DNA共价修饰的酶，另一类是利用ATP水解产生的能量机械改变染色质结构的酶。这两类酶通常都存在于大型蛋白质复合物中。在本综述中，我们描述了两种这样的复合物：多梳抑制复合物2（PRC2），其催化亚基为蛋白质甲基转移酶EZH2，以及ATP依赖的染色质重塑因子开关/蔗糖不发酵复合物（SWI/SNF）。EZH2催化组蛋白H3上赖氨酸27的甲基化，这是一种与抑制性异染色质相关的共价染色质修饰。相比之下，SWI/SNF的催化活性会导致与活跃转录相关的开放染色质状态。在本综述中，我们讨论了这两种复合物的生化特性，概述了它们的调控原则，并描述了它们在正常发育中的相反作用，而在癌症等疾病环境中这些作用可能会受到干扰。
