Regulation of MBD1-mediated transcriptional repression by SUMO and PIAS proteins (Retracted article. See vol. 38, 2019)
Regulation of MBD1-mediated transcriptional repression by SUMO and PIAS proteins (Retracted article. See vol. 38, 2019)
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DOI：
10.1038/sj.emboj.7601404
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发表时间：
2006-11-15
期刊：
影响因子：
11.4
通讯作者：
Stancheva, Irina
中科院分区：
文献类型：
--
作者：
Lyst, Matthew J.;Nan, Xinsheng;Stancheva, Irina
在哺乳动物细胞中，DNA甲基化与遗传性和稳定的基因阻遏相关，部分由甲基CpG结合结构域（MBD）蛋白介导，该蛋白招募辅阻遏物以修饰染色质。MBD 1蛋白是MBD家族的成员，与SETDB 1组蛋白甲基化酶形成复合物，通过组蛋白H3的赖氨酸9的甲基化来沉默靶启动子处的转录。MBD 1介导的转录抑制是如何调节的，目前尚不清楚。在这里，我们表明，MBD 1是由PIAS 1（激活STAT 1的蛋白质抑制剂）和PIAS 3 E3 SUMO（小泛素样修饰剂）-连接酶类小泛素化的目标，在两个保守的赖氨酸残基内的MBD 1的C-末端。虽然类小泛素化MBD 1结合甲基化DNA，但它不与SETDB 1结合成复合物，并且在HeLa细胞中不能有效抑制靶基因p53 BP 2的转录。我们的数据表明，MBD 1的转录沉默是由PIAS介导的SUMO 1的结合，拮抗与SETDB 1的抑制复合物的形成。
In mammalian cells, DNA methylation is associated with heritable and stable gene repression, mediated in part by methyl-CpG-binding domain (MBD) proteins that recruit corepressors to modify chromatin. MBD1 protein, a member of the MBD family, forms a complex with SETDB1 histone methylase to silence transcription at target promoters by methylation of lysine 9 of histone H3. How MBD1-mediated transcriptional repression is regulated is currently unknown. Here we show that MBD1 is a target for sumoylation by PIAS1 (Protein Inhibitors of Activated STAT 1) and PIAS3 E3 SUMO (small ubiquitin-like modifier)-ligases, at two conserved lysine residues within the C-terminus of MBD1. Although sumoylated MBD1 binds to methylated DNA, it does not incorporate into a complex with SETDB1 and does not efficiently repress transcription of a target gene, p53BP2, in HeLa cells. Our data suggest that transcriptional silencing by MBD1 is regulated by a PIAS-mediated conjugation of SUMO1, which antagonizes the formation of a repressive complex with SETDB1.