Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, United States.
Elife. 2020 Jan 10;9:e53199. doi: 10.7554/eLife.53199.
Methylation of histone H3K4 is a hallmark of actively transcribed genes that depends on mono-ubiquitination of histone H2B (H2B-Ub). H3K4 methylation in yeast is catalyzed by Set1, the methyltransferase subunit of COMPASS. We report here the cryo-EM structure of a six-protein core COMPASS subcomplex, which can methylate H3K4 and be stimulated by H2B-Ub, bound to a ubiquitinated nucleosome. Our structure shows that COMPASS spans the face of the nucleosome, recognizing ubiquitin on one face of the nucleosome and methylating H3 on the opposing face. As compared to the structure of the isolated core complex, Set1 undergoes multiple structural rearrangements to cement interactions with the nucleosome and with ubiquitin. The critical Set1 RxxxRR motif adopts a helix that mediates bridging contacts between the nucleosome, ubiquitin and COMPASS. The structure provides a framework for understanding mechanisms of trans-histone cross-talk and the dynamic role of H2B ubiquitination in stimulating histone methylation.
组蛋白 H3K4 的甲基化是活跃转录基因的标志，依赖于组蛋白 H2B 的单泛素化 (H2B-Ub)。酵母中的 H3K4 甲基化由 COMPASS 的甲基转移酶亚基 Set1 催化。我们在这里报告了一个六蛋白核心 COMPASS 亚基复合物的冷冻电镜结构，该复合物可以甲基化 H3K4，并被结合到泛素化核小体上的 H2B-Ub 刺激。我们的结构表明，COMPASS 跨越核小体的表面，在核小体的一个面上识别泛素，并在对面甲基化 H3。与分离的核心复合物的结构相比，Set1 经历了多个结构重排，以固定与核小体和泛素的相互作用。关键的 Set1 RxxxRR 基序采用一个螺旋，介导核小体、泛素和 COMPASS 之间的桥接接触。该结构为理解跨组蛋白相互作用的机制以及 H2B 泛素化在刺激组蛋白甲基化中的动态作用提供了一个框架。
