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.

中文翻译：

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COMPASS识别H2B泛素化核小体的结构基础

组蛋白H3K4的甲基化是依赖于组蛋白H2B（H2B-Ub）单泛素化的活跃转录基因的标志。酵母中的H3K4甲基化由Set1（COMPASS的甲基转移酶亚基）催化。我们在这里报告的六蛋白核心COMPASS亚复合物的冷冻EM结构，它可以甲基化H3K4，并受H2B-Ub刺激，与泛素化核小体结合。我们的结构表明，COMPASS跨越了核小体的整个表面，在核小体的一个面上识别了泛素，而在相反的一面上识别了H3。与分离的核心复合物的结构相比，Set1经历了多种结构重排，以巩固与核小体和泛素的相互作用。关键的Set1 RxxxRR基序采用螺旋介导核小体，遍在蛋白和COMPASS之间的桥接接触。