2011年1月14日，我所朱冰实验室在 The Journal of Biological chemistry 上在线发表题为“H3K36 methylation antagonizes PRC2 mediated H3K27 methylation”的文章。该文章主要报道了组蛋白H3第36位赖氨酸甲基化可以拮抗组蛋白甲基化酶PRC2对H3第27位赖氨酸进行修饰。
PRC2复合物所介导的组蛋白H3第27位赖氨酸甲基化修饰对于基因的转录起着重要的调节作用。PRC2复合物所介导的27位赖氨酸甲基化修饰可以在染色质上蔓延从而形成区域性的抑制型染色质环境。所以，一个很重要的问题就是染色质上哪些组分能够拮抗这种蔓延。在本项研究中我们发现在HeLa细胞中，H3第27位赖氨酸的三甲基化修饰很少与H3第36赖氨酸的高阶甲基化（二甲基化合三甲基化）修饰共存于同一条多肽上。并且通过生化实验证明含有H3第36位赖氨酸甲基化修饰的核小体可以抑制PRC2复合物在其上的活性。最后，我们还证明了一个已知的PRC2拮抗蛋白ASH1，是一个H3第36位赖氨酸专一性的组蛋白甲基化酶。
论文的共同第一作者是我所与中国农业大学联合培养的博士生袁文和我所与协和医科大学联合培养的博士生徐墨。论文的其他作者还包括我所博士生黄畅和刘楠，以及蛋白质中心陈涉博士。 朱冰博士是论文的通讯作者。该项目由科技部和北京市资助。（生物谷Bioon.com）
生物谷推荐原文出处：
The Journal of Biological chemistry doi: 10.1074/jbc.M110.194027
H3K36 methylation antagonizes PRC2 mediated H3K27 methylation
Wen Yuan1, Mo Xu2, Chang Huang1, Nan Liu3, She Chen4 and Bing Zhu4,*
Abstract
H3K27 methylation mediated by the histone methyltransferase complex PRC2 is critical for transcriptional regulation, Polycomb silencing, Drosophila segmentation, mammalian X chromosome inactivation and cancer. PRC2-mediated H3K27 methylation can spread along the chromatin and propagate the repressive chromatin environment; thus, chromatin components that antagonize PRC2's activity are important for restraining Polycomb silencing. Here we report that in HeLa cells, H3 histones unmethylated at K36 are mostly methylated at K27, with the exception of newly synthesized H3. In addition, K27me3 rarely co-exists with K36me2 or K36me3 on the same histone H3 polypeptide. Moreover, PRC2 activity is greatly inhibited on nucleosomal substrates with pre-installed H3K36 methylation. These findings collectively identify H3K36 methylation as a chromatin component that restricts the PRC2-mediated spread of H3K27 methylation. Finally, we provide evidence that the controversial histone lysine methyltransferase Ash1, a known Trithorax group protein that antagonizes Polycomb silencing in vivo, is an H3K36-specific dimethylase, not an H3K4 methylase, further supporting the role of H3K36 methylation in antagonizing PRC2-mediated H3K27 methylation.
