Klein Brianna J, Simithy Johayra, Wang Xiaolu, Ahn JaeWoo, Andrews Forest H, Zhang Yi, Côté Jacques, Shi Xiaobing, Garcia Benjamin A, Kutateladze Tatiana G
Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Epigenetics Program, Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Structure. 2017 Apr 4;25(4):650-654.e2. doi: 10.1016/j.str.2017.02.003. Epub 2017 Mar 9.
The monocytic leukemia zinc-finger protein-related factor (MORF) is a transcriptional coactivator and a catalytic subunit of the lysine acetyltransferase complex implicated in cancer and developmental diseases. We have previously shown that the double plant homeodomain finger (DPF) of MORF is capable of binding to acetylated histone H3. Here we demonstrate that the DPF of MORF recognizes many newly identified acylation marks. The mass spectrometry study provides comprehensive analysis of H3K14 acylation states in vitro and in vivo. The crystal structure of the MORF DPF-H3K14butyryl complex offers insight into the selectivity of this reader toward lipophilic acyllysine substrates. Together, our findings support the mechanism by which the acetyltransferase MORF promotes spreading of histone acylation.
单核细胞白血病锌指蛋白相关因子（MORF）是一种转录共激活因子，也是赖氨酸乙酰转移酶复合物的催化亚基，与癌症和发育性疾病有关。我们之前已经表明，MORF的双植物同源结构域指（DPF）能够结合乙酰化组蛋白H3。在此我们证明，MORF的DPF能识别许多新发现的酰化标记。质谱研究提供了对体外和体内H3K14酰化状态的全面分析。MORF DPF-H3K14丁酰复合物的晶体结构揭示了该读取器对亲脂性酰基赖氨酸底物的选择性。总之，我们的研究结果支持了乙酰转移酶MORF促进组蛋白酰化扩散的机制。
