H3K14 ubiquitylation promotes H3K9 methylation for heterochromatin assembly
H3K14 ubiquitylation promotes H3K9 methylation for heterochromatin assembly
复制标题
DOI：
10.15252/embr.201948111
复制
发表时间：
2019-10-04
期刊：
影响因子：
7.7
通讯作者：
Nakayama, Jun-ichi
中科院分区：
文献类型：
--
作者：
Oya, Eriko;Nakagawa, Reiko;Nakayama, Jun-ichi
组蛋白H3在赖氨酸9（H3 K9 me）的甲基化，由甲基转移酶Clr 4/SUV 39 H进行，是异染色质组装的关键事件。在裂殖酵母中，Clr 4与泛素E3连接酶Cul 4一起形成Clr 4甲基转移酶复合物（CLRC），其生理靶点和生物学作用目前尚不清楚。在这里，我们表明，CLRC依赖的H3泛素化调节Clr 4的甲基转移酶活性。亲和纯化的CLRC泛素化组蛋白H3，质谱和突变分析表明，H3赖氨酸14（H3 K14）是复合物的首选目标。染色质免疫沉淀分析表明，H3 K14泛素化（H3 K14 ub）与富含H3 K9 me的染色质密切相关。值得注意的是，CLRC介导的H3泛素化通过Clr 4促进H3 K9 me，表明H3泛素化与H3 K9 me的建立和/或维持密切相关。这些发现证明了组蛋白泛素化和甲基化之间的串扰机制，参与异染色质组装。
The methylation of histone H3 at lysine 9 (H3K9me), performed by the methyltransferase Clr4/SUV39H, is a key event in heterochromatin assembly. In fission yeast, Clr4, together with the ubiquitin E3 ligase Cul4, forms the Clr4 methyltransferase complex (CLRC), whose physiological targets and biological role are currently unclear. Here, we show that CLRC-dependent H3 ubiquitylation regulates Clr4's methyltransferase activity. Affinity-purified CLRC ubiquitylates histone H3, and mass spectrometric and mutation analyses reveal that H3 lysine 14 (H3K14) is the preferred target of the complex. Chromatin immunoprecipitation analysis shows that H3K14 ubiquitylation (H3K14ub) is closely associated with H3K9me-enriched chromatin. Notably, the CLRC-mediated H3 ubiquitylation promotes H3K9me by Clr4, suggesting that H3 ubiquitylation is intimately linked to the establishment and/or maintenance of H3K9me. These findings demonstrate a cross-talk mechanism between histone ubiquitylation and methylation that is involved in heterochromatin assembly.