Tao Ye, Zhong Chen, Zhu Junjun, Xu Shutong, Ding Jianping
National Center for Protein Science Shanghai, State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, and University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
School of Life Science and Technology, ShanghaiTech University, 100 Haike Road, Shanghai 201210, China.
Nucleic Acids Res. 2017 Jun 2;45(10):5707-5719. doi: 10.1093/nar/gkx142.
HBO1, a member of the MYST family of histone acetyltransferases (HATs), is required for global acetylation of histone H3K14 and embryonic development. It functions as a catalytic subunit in multisubunit complexes comprising a BRPF1/2/3 or JADE1/2/3 scaffold protein, and two accessory proteins. BRPF2 has been shown to be important for the HAT activity of HBO1 toward H3K14. Here we demonstrated that BRPF2 can regulate the HAT activity of HBO1 toward free H3 and H4, and nucleosomal H3. Particularly, a short N-terminal region of BRPF2 is sufficient for binding to HBO1 and can potentiate its activity toward H3K14. The crystal structure of the HBO1 MYST domain in complex with this segment of BRPF2 together with the biochemical and cell biological data revealed the key residues responsible for the HBO1-BRPF2 interaction. Our structural and functional data together indicate that the N-terminal region of BRPF2 plays an important role in the binding of HBO1 and a minor role in the binding of nucleosomes, which provide new mechanistic insights into the regulation of the HAT activity of HBO1 by BRPF2.
HBO1是组蛋白乙酰转移酶（HATs）MYST家族的成员之一，是组蛋白H3K14全局乙酰化和胚胎发育所必需的。它在包含BRPF1/2/3或JADE1/2/3支架蛋白以及两个辅助蛋白的多亚基复合物中作为催化亚基发挥作用。BRPF2已被证明对HBO1针对H3K14的HAT活性很重要。在此我们证明，BRPF2可以调节HBO1针对游离H3和H4以及核小体H3的HAT活性。特别地，BRPF2的一个短N端区域足以与HBO1结合，并能增强其针对H3K14的活性。HBO1 MYST结构域与BRPF2的这一片段形成复合物的晶体结构，连同生化和细胞生物学数据，揭示了负责HBO1 - BRPF2相互作用的关键残基。我们的结构和功能数据共同表明，BRPF2的N端区域在与HBO1的结合中起重要作用，而在与核小体的结合中起次要作用，这为BRPF2对HBO1的HAT活性调控提供了新的机制见解。
