Du Qian, Luu Phuc-Loi, Stirzaker Clare, Clark Susan J
Epigenetics Research Laboratory, Genomics & Epigenetics Division, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia.
St Vincent's Clinical School, University of NSW, Darlinghurst, NSW 2010, Australia.
Epigenomics. 2015;7(6):1051-73. doi: 10.2217/epi.15.39. Epub 2015 Apr 30.
How DNA methylation is interpreted and influences genome regulation remains largely unknown. Proteins of the methyl-CpG-binding domain (MBD) family are primary candidates for the readout of DNA methylation as they recruit chromatin remodelers, histone deacetylases and methylases to methylated DNA associated with gene repression. MBD protein binding requires both functional MBD domains and methyl-CpGs; however, some MBD proteins also bind unmethylated DNA and active regulatory regions via alternative regulatory domains or interaction with the nucleosome remodeling deacetylase (NuRD/Mi-2) complex members. Mutations within MBD domains occur in many diseases, including neurological disorders and cancers, leading to loss of MBD binding specificity to methylated sites and gene deregulation. Here, we summarize the current state of knowledge about MBD proteins and their role as readers of the epigenome.
DNA甲基化如何被解读以及如何影响基因组调控在很大程度上仍然未知。甲基化CpG结合域（MBD）家族的蛋白质是读取DNA甲基化的主要候选者，因为它们会将染色质重塑因子、组蛋白去乙酰化酶和甲基化酶招募到与基因抑制相关的甲基化DNA上。MBD蛋白结合既需要功能性MBD结构域，也需要甲基化的CpG；然而，一些MBD蛋白还通过其他调控结构域或与核小体重塑去乙酰化酶（NuRD/Mi-2）复合物成员相互作用，与未甲基化的DNA和活跃调控区域结合。MBD结构域内的突变发生在许多疾病中，包括神经疾病和癌症，导致MBD对甲基化位点的结合特异性丧失以及基因失调。在这里，我们总结了关于MBD蛋白及其作为表观基因组读取器的作用的当前知识状态。
