Department of Cellular & Molecular Medicine, College of Medicine, Chosun University, Gwangju, 61452, South Korea.
Department of Food and Nutrition, Chonnam National University, Gwangju, 61186, South Korea.
Nat Commun. 2020 Jun 19;11(1):3140. doi: 10.1038/s41467-020-16907-0.
MeCP2 plays a multifaceted role in gene expression regulation and chromatin organization. Interaction between MeCP2 and methylated DNA in the regulation of gene expression is well established. However, the widespread distribution of MeCP2 suggests it has additional interactions with chromatin. Here we demonstrate, by both biochemical and genomic analyses, that MeCP2 directly interacts with nucleosomes and its genomic distribution correlates with that of H3K27me3. In particular, the methyl-CpG-binding domain of MeCP2 shows preferential interactions with H3K27me3. We further observe that the impact of MeCP2 on transcriptional changes correlates with histone post-translational modification patterns. Our findings indicate that MeCP2 interacts with genomic loci via binding to DNA as well as histones, and that interaction between MeCP2 and histone proteins plays a key role in gene expression regulation.
MECP2 在基因表达调控和染色质组织中发挥着多方面的作用。MECP2 与甲基化 DNA 的相互作用在基因表达调控中已得到充分证实。然而,MECP2 的广泛分布表明它与染色质有额外的相互作用。在这里,我们通过生化和基因组分析证明,MECP2 直接与核小体相互作用,其基因组分布与 H3K27me3 的分布相关。特别是,MECP2 的甲基-CpG 结合域与 H3K27me3 表现出优先相互作用。我们进一步观察到,MECP2 对转录变化的影响与组蛋白翻译后修饰模式相关。我们的研究结果表明,MECP2 通过与 DNA 以及组蛋白结合来与基因组位点相互作用,并且 MECP2 与组蛋白蛋白之间的相互作用在基因表达调控中起着关键作用。