由SETD2双重染色质和细胞骨架重塑。
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公园IY,鲍威尔RT Tripathi DN,溪谷R, Ho, Blasius TL,蒋介石YC,戴维斯IJ, Fahey CC,黑客KE, Verhey KJ,贝德福德太,Jonasch E, Rathmell周,沃克CL
由SETD2双重染色质和细胞骨架重塑。
细胞。2016年8月11日,166 (4):950 - 62。doi: 10.1016 / j.cell.2016.07.005。
- PubMed ID
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27518565 (在PubMed]
- 文摘
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转译后的修改(天车)的微管蛋白指定专门的细胞功能和微管组成所谓的“微管蛋白的代码”。PTMs of histones comprise an analogous "histone code," although the "readers, writers, and erasers" of the cytoskeleton and epigenome have heretofore been distinct. We show that methylation is a PTM of dynamic microtubules and that the histone methyltransferase SET-domain-containing 2 (SETD2), which is responsible for H3 lysine 36 trimethylation (H3K36me3) of histones, also methylates alpha-tubulin at lysine 40, the same lysine that is marked by acetylation on microtubules. Methylation of microtubules occurs during mitosis and cytokinesis and can be ablated by SETD2 deletion, which causes mitotic spindle and cytokinesis defects, micronuclei, and polyploidy. These data now identify SETD2 as a dual-function methyltransferase for both chromatin and the cytoskeleton and show a requirement for methylation in maintenance of genomic stability and the integrity of both the tubulin and histone codes.