Role of the RB1 family in stabilizing histone methylation at constitutive heterochromatin
Role of the RB1 family in stabilizing histone methylation at constitutive heterochromatin
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DOI：
10.1038/ncb1235
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发表时间：
2005-04-01
影响因子：
21.3
通讯作者：
Blasco, MA
中科院分区：
文献类型：
--
作者：
Gonzalo, S;García-Cao, M;Blasco, MA
在这里，我们展示了RB 1家族蛋白在指导完全异染色质形成中的作用。RB 1（视网膜母细胞瘤1）、RBL 1（视网膜母细胞瘤样1）和RBL 2（视网膜母细胞瘤样2）三重缺陷的小鼠胚胎成纤维细胞--称为TKO细胞--显示出明显的基因组不稳定性，这与DNA甲基化降低、组蛋白H3乙酰化增加和组蛋白H4赖氨酸20（H4 K20）三甲基化降低相一致。染色质免疫沉淀显示，H4 K20三甲基化在臂间和端粒染色质特异性降低。这些缺陷与E2 F家族功能无关。事实上，我们显示了RB 1蛋白与H4 K20三甲基化酶Suv 4 - 20 h1和Suv 4 - 20 h2之间的直接相互作用，表明RB 1家族在通过这些组蛋白甲基转移酶控制H4 K20三甲基化中具有作用。这些观察结果表明，RB 1家族参与维持整体染色质结构，特别是组成性异染色质，将肿瘤抑制和染色质的表观遗传定义联系起来。
Here, we show a role for the RB1 family proteins in directing full heterochromatin formation. Mouse embryonic fibroblasts that are triply deficient for RB1 (retinoblastoma 1), RBL1 (retinoblastoma-like 1) and RBL2 (retinoblastoma-like 2) - known as TKO cells - show a marked genomic instability, which is coincidental with decreased DNA methylation, increased acetylation of histone H3 and decreased tri-methylation of histone H4 at lysine 20 (H4K20). Chromatin immunoprecipitation showed that H4K20 tri-methylation was specifically decreased at pericentric and telomeric chromatin. These defects are independent of E2F family function. Indeed, we show a direct interaction between the RB1 proteins and the H4K20 tri-methylating enzymes Suv4-20h1 and Suv4-20h2, indicating that the RB1 family has a role in controlling H4K20 tri-methylation by these histone methyltransferases. These observations indicate that the RB1 family is involved in maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin, linking tumour suppression and the epigenetic definition of chromatin.