Department of Molecular Biophysics & Biochemistry, Yale University, New Haven, CT 06520, USA.
Nucleic Acids Res. 2010 Jun;38(11):3503-11. doi: 10.1093/nar/gkq081. Epub 2010 Feb 16.
The histone code hypothesis predicts that the post-translational modification of histones can bring about distinct chromatin states, and it therefore serves a key regulatory role in chromatin biology. The impact of one mark on another has been termed cross-talk. Some marks are mutually exclusive, while others act in concert. As multiple marks contributing to one outcome are generally brought about by complexes containing multiple catalytic and binding domains, it appears regulation of chromatin involves a web of writers and readers of histone modifications, chromatin remodeling activities and DNA methylation. Here, we focus on the protein lysine methyltransferases G9a and GLP as examples of this extended cross-talk. G9a and GLP can catalyze the formation of and bind to the same methyl mark via distinct domains. We consider the impact of other histone modifications on G9a/GLP activity and the coordination of activities within G9a/GLP containing complexes. We evaluate the potential impact of product binding on product specificity and on maintenance and propagation of the methyl mark. Lastly, we examine the recruitment of other silencing factors by G9a/GLP. Regulated assembly of specific complexes around key marks may reinforce or alter the biological outcome associated with given histone modifications.
组蛋白密码假说预测组蛋白的翻译后修饰可以带来不同的染色质状态，因此在染色质生物学中起着关键的调节作用。一个标记对另一个标记的影响被称为串扰。有些标记是相互排斥的，而有些则协同作用。由于对一个结果做出贡献的多个标记通常是由包含多个催化和结合结构域的复合物引起的，因此似乎染色质的调节涉及到组蛋白修饰、染色质重塑活性和 DNA 甲基化的一系列写入器和读取器。在这里，我们以 G9a 和 GLP 这两种蛋白赖氨酸甲基转移酶为例，探讨这种扩展的串扰。G9a 和 GLP 可以通过不同的结构域催化和结合相同的甲基标记。我们考虑了其他组蛋白修饰对 G9a/GLP 活性的影响以及 G9a/GLP 包含的复合物内活性的协调。我们评估了产物结合对产物特异性以及对甲基标记的维持和传播的潜在影响。最后，我们研究了 G9a/GLP 对其他沉默因子的招募。特定复合物围绕关键标记的调节组装可能会增强或改变与特定组蛋白修饰相关的生物学结果。
