The ski protein family is required for MeCP2-mediated transcriptional repression
The ski protein family is required for MeCP2-mediated transcriptional repression
复制标题
DOI：
10.1074/jbc.m105747200
复制
发表时间：
2001-09-07
影响因子：
4.8
通讯作者：
Ishii, S
中科院分区：
文献类型：
--
作者：
Kokura, K;Kaul, SC;Ishii, S
DNA甲基化对小鼠的发育是必不可少的，并在X染色体失活和基因组印记中发挥重要作用。MeCP2是甲基CpG结合蛋白家族的创始成员。MeCP2直接与共抑制物mSin3结合，后者与I类组蛋白脱乙酰酶相互作用，将它们招募到甲基CpG区域以抑制转录。在这里，我们报告了MeCP2除了mSin3A外，还直接与两个共抑制物c-Ski和N-COR结合，并且由c-ski原癌基因编码的c-Ski是MeCP2介导的转录抑制所必需的。C-Ski的两个区域，包括C-末端卷曲区域，与MeCP2分子中心的转录抑制结构域相互作用。C-Ski和MeCP2的免疫染色信号在核异染色质区域重叠，表明这两种蛋白共同定位。由Gal4-MeCP2融合蛋白介导的转录抑制程度被假定的显性阴性形式c-Ski的过度表达所取消。此外，注射抗c-Ski和Sno的抗体几乎完全取消了Gal4-MeCP2融合蛋白介导的转录抑制。这些结果表明，SKI基因家族参与了甲基CpG介导的转录抑制。
DNA methylation is essential for development in the mouse and plays an important role in inactivation of the X chromosome and genomic imprinting. MeCP2 is the founder member of a family of methyl-CpG-binding proteins. MeCP2 directly binds to the co-repressor mSin3, which interacts with class I histone deacetylase, recruiting them to methyl-CpG regions to suppress transcription. Here, we report that MeCP2 directly binds to two co-repressors, c-Ski and N-CoR, in addition to mSin3A, and that the c-Ski, which is encoded by the c-ski proto-onocogene, is required for MeCP2-mediated transcriptional repression. The two regions of c-Ski, including the C-terminal coiled-coil region, interact with the transcriptional repression domain in the center of the MeCP2 molecule. The immunostaining signals for c-Ski and MeCP2 overlap in the nuclear heterochromatin region, suggesting the co-localization of the two proteins. The degree of transcriptional repression mediated by a Gal4-MeCP2 fusion protein was abrogated by overexpression of the putative dominant negative form of c-Ski. Furthermore, injection of antibodies against c-Ski and Sno almost completely abolished the transcriptional repression mediated by the Gal4-MeCP2 fusion protein. These results suggest that the ski gene family is involved in methyl CpG-mediated transcriptional repression.