Dr. Bing Zhu's group found that Histone H2A ubiquitination inhibits the enzymatic activity of H3 Lysine 36 methyltransferases.

    On September 10, 2013, Dr. Bing Zhu's lab published an online article titled "Histone H2A ubiquitination inhibits the enzymatic activity of H3 Lysine 36 methyltransferases" in The Journal of Biological Chemistry.

    Many kinds of post translational modifications (PTMs) occur on histones, and the interplay among different PTMs contributes to transcriptional regulation. Previously, Zhu lab discovered that transcriptional repression associated H3K27me3 modification does not co-exist with transcriptional activation associated H3K36me2/3 modifications on the same histone H3 polypeptides. Zhu lab also found that H3K36me2/3 directly inhibits H3K27 methyltransferase PRC2 and a classic PRC2 antagonist Ash1 is an H3K36 methyltransferase. This work was published in The Journal of Biological Chemistry in 2011 and was designated as the Best JBC paper of 2011.

    In the previous study, Zhu lab also found that H3K27me3 does not affect histone methyltransferases targeting H3K36. Therefore, it remains not fully understood why H3K27me3 cannot coexist with H3K36me2/3 in vivo.

    H2A mono-ubiquitination and H3K27me3 are both reaction products of Polycomb group proteins and they often coexist. In this study, we attempted to explain the incompatibility between H3K27me3 and H3K36me2/3 from the angle of H2A mono-ubiquitination. In this study, Zhu lab developed a simple method to purify milligram quantities of mono-ubiquitinated histone H2A; then compared the activity of different histone methyltransferases on nucleosomes containing mono-ubiquitinated histone H2A or unmodified histone H2A, and found that only H3K36-specific methyltransferases were inhibited by H2A mono-ubiquitination. Together with previous findings, this study helps to understand the interplay between H3K36 methylation and Polycomb modifications.

    Dr. Gang Yuan is the first author of this paper. Ben Ma, Dr. Wen Yuan and Dr. Zhuqiang Zhang also made important contributions to this paper. Other co-authors include Li Feng, Xiaojun Ding, Dr. She Chen from NIBS, and Drs. Ping Chen and Guohong Li from the Institute of Biophysics, Chinese Academy of Sciences and Dr. Xiaohua Shen from the Tsinghua University. The corresponding author is Dr. Bing Zhu. This study was supported by the Howard Hughes Medical Institute International Early Career Scientist Program, grants from the Chinese Ministry of Science and Technology, and the Beijing Municipal Government.