Zhang Wen-juan, Wu Xiao-nan, Shi Tao-tao, Xu Huan-teng, Yi Jia, Shen Hai-feng, Huang Ming-feng, Shu Xing-yi, Wang Fei-fei, Peng Bing-ling, Xiao Rong-quan, Gao Wei-wei, Ding Jian-cheng, Liu Wen
School of Pharmaceutical Sciences, Xiamen University, Xiang'an South Road, Xiamen, Fujian 361102, China.
College of Chemistry and Chemical Engineering, Xiamen University, No. 422 Siming South Road, Xiamen, Fujian 361105, China.
Sci Rep. 2016 Feb 23;6:21718. doi: 10.1038/srep21718.
Yin Yang 1 (YY1) is a multifunctional transcription factor shown to be critical in a variety of biological processes. Although it is regulated by multiple types of post-translational modifications (PTMs), whether YY1 is methylated, which enzyme methylates YY1, and hence the functional significance of YY1 methylation remains completely unknown. Here we reported the first methyltransferase, SET7/9 (KMT7), capable of methylating YY1 at two highly conserved lysine (K) residues, K173 and K411, located in two distinct domains, one in the central glycine-rich region and the other in the very carboxyl-terminus. Functional studies revealed that SET7/9-mediated YY1 methylation regulated YY1 DNA-binding activity both in vitro and at specific genomic loci in cultured cells. Consistently, SET7/9-mediated YY1 methylation was shown to involve in YY1-regulated gene transcription and cell proliferation. Our findings revealed a novel regulatory strategy, methylation by lysine methyltransferase, imposed on YY1 protein, and linked YY1 methylation with its biological functions.
阴阳1（YY1）是一种多功能转录因子，已证明其在多种生物学过程中至关重要。尽管它受多种类型的翻译后修饰（PTM）调控，但YY1是否被甲基化、哪种酶使YY1甲基化，以及YY1甲基化的功能意义仍然完全未知。在此，我们报道了首个能够使YY1在位于两个不同结构域的两个高度保守的赖氨酸（K）残基K173和K411处发生甲基化的甲基转移酶SET7/9（KMT7），其中一个结构域位于富含甘氨酸的中央区域，另一个位于非常靠近羧基末端的位置。功能研究表明，SET7/9介导的YY1甲基化在体外以及在培养细胞的特定基因组位点均调控YY1的DNA结合活性。同样，SET7/9介导的YY1甲基化被证明参与YY1调控的基因转录和细胞增殖。我们的研究结果揭示了一种施加于YY1蛋白上的由赖氨酸甲基转移酶介导的新型调控策略，即甲基化，并将YY1甲基化与其生物学功能联系起来。
