SMYD5 catalyzes histone H3 lysine 36 trimethylation at promoters.
SMYD5 catalyzes histone H3 lysine 36 trimethylation at promoters.
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SMYD5 在启动子处催化组蛋白 H3 赖氨酸 36 三甲基化
DOI：
10.1038/s41467-022-30940-1
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发表时间：
2022-06-09
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
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作者：
组蛋白标记是表观遗传信息的载体，调节基因表达。在哺乳动物细胞中，H3 K36 me 3主要由基因体区域的SETD 2催化。在这里，我们发现，除了基因体区域，H3 K36 me 3在原代细胞中的启动子富集。通过筛选，我们确定SMYD 5，这是招募到染色质的RNA聚合酶II，作为一个甲基转移酶催化H3 K36 me 3的启动子。SMYD 5的酶活性取决于其C-末端富含谷氨酸的结构域。全长Smyd 5的过表达，但不是C-末端结构域截短的Smyd 5，恢复H3 K36 me 3在Smyd 5敲除细胞的启动子。此外，Smyd 5表达升高有助于肝细胞癌的肿瘤发生。总之，我们的研究结果将SMYD 5确定为调节基因表达的启动子处的H3 K36 me 3甲基转移酶，为H3 K36 me 3的定位和功能提供了见解。SETD 2甲基化哺乳动物细胞基因体中的组蛋白H3 K36 me 3。在这里，作者表明H3 K36 me 3也在启动子区域富集，并且这种甲基化是由SMYD 5进行的，SMYD 5由RNA聚合酶II募集。他们还表明SMYD 5在肝癌中升高，并与基因表达的变化相关。
Histone marks, carriers of epigenetic information, regulate gene expression. In mammalian cells, H3K36me3 is mainly catalyzed by SETD2 at gene body regions. Here, we find that in addition to gene body regions, H3K36me3 is enriched at promoters in primary cells. Through screening, we identify SMYD5, which is recruited to chromatin by RNA polymerase II, as a methyltransferase catalyzing H3K36me3 at promoters. The enzymatic activity of SMYD5 is dependent on its C-terminal glutamic acid-rich domain. Overexpression of full-length Smyd5, but not the C-terminal domain-truncated Smyd5, restores H3K36me3 at promoters in Smyd5 knockout cells. Furthermore, elevated Smyd5 expression contributes to tumorigenesis in liver hepatocellular carcinoma. Together, our findings identify SMYD5 as the H3K36me3 methyltransferase at promoters that regulates gene expression, providing insights into the localization and function of H3K36me3. SETD2 methylates histone H3K36me3 in gene bodies in mammalian cells. Here the authors show H3K36me3 is also enriched at the promoter regions, and that this methylation is carried out by SMYD5, which is recruited by RNA polymerase II. They furthermore show SMYD5 is elevated in liver cancer and is correlated with changes in gene expression.
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影响因子：
--
作者：
Huang C;Zhu B
通讯作者：
Zhu B
影响因子：
10.5
作者：
Guo X;Zhao Y;Yan H;Yang Y;Shen S;Dai X;Ji X;Ji F;Gong XG;Li L;Bai X;Feng XH;Liang T;Ji J;Chen L;Wang H;Zhao B
通讯作者：
Zhao B
人 TFIIH 激酶 CDK7 调节转录相关的染色质修饰。
影响因子：
8.8
作者：
Ebmeier CC;Erickson B;Allen BL;Allen MA;Kim H;Fong N;Jacobsen JR;Liang K;Shilatifard A;Dowell RD;Old WM;Bentley DL;Taatjes DJ
通讯作者：
Taatjes DJ
影响因子：
4.6
作者：
Fujii T;Tsunesumi S;Sagara H;Munakata M;Hisaki Y;Sekiya T;Furukawa Y;Sakamoto K;Watanabe S
通讯作者：
Watanabe S
影响因子：
4.5
作者：
Langdon WB
通讯作者：
Langdon WB