Feng Q, Zhang Y
Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, North Carolina 27599-7295, USA.
Genes Dev. 2001 Apr 1;15(7):827-32. doi: 10.1101/gad.876201.
Histone deacetylation plays an important role in methylated DNA silencing. Recent studies indicated that the methyl-CpG-binding protein, MBD2, is a component of the MeCP1 histone deacetylase complex. Interestingly, MBD2 is able to recruit the nucleosome remodeling and histone deacetylase, NuRD, to methylated DNA in vitro. To understand the relationship between the MeCP1 complex and the NuRD complex, we purified the MeCP1 complex to homogeneity and found that it contains 10 major polypeptides including MBD2 and all of the known NuRD components. Functional analysis of the purified MeCP1 complex revealed that it preferentially binds, remodels, and deacetylates methylated nucleosomes. Thus, our study defines the MeCP1 complex, and provides biochemical evidence linking nucleosome remodeling and histone deacetylation to methylated gene silencing.
组蛋白去乙酰化在甲基化DNA沉默中起重要作用。最近的研究表明,甲基化CpG结合蛋白MBD2是MeCP1组蛋白去乙酰化酶复合物的一个组成部分。有趣的是,MBD2在体外能够将核小体重塑和组蛋白去乙酰化酶NuRD募集到甲基化DNA上。为了了解MeCP1复合物与NuRD复合物之间的关系,我们将MeCP1复合物纯化至同质,并发现它包含10种主要多肽,包括MBD2以及所有已知的NuRD组分。对纯化后的MeCP1复合物的功能分析表明,它优先结合、重塑并使甲基化核小体去乙酰化。因此,我们的研究定义了MeCP1复合物,并提供了将核小体重塑和组蛋白去乙酰化与甲基化基因沉默联系起来的生化证据。