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首页> 外文期刊>Biochimica et Biophysica Acta. Gene Regulatory Mechanisms >CpG dinucleotide positioning patterns determine the binding affinity of methyl-binding domain to nucleosomes
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CpG dinucleotide positioning patterns determine the binding affinity of methyl-binding domain to nucleosomes

机译：CpG二核苷酸定位模式确定甲基结合结构域与核体的结合亲和力

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摘要

The methyl-binding domain of MBD1 is a common methyl CpG binding motif and has been linked to transcriptional repression. Understanding the dynamics of MBD1 binding to nucleosomal DNA is crucial, but the molecular interactions between MBD1 and chromatin remain elusive. In this study, we found the binding of MBD1 to nucleosomes demonstrates sequence preferences depending on the position of the methyl groups on the nucleosome. Specifically, binding was favored at (me)CpG sites in the dyad proximal region and facing towards the histone octamers. At locations where the (me)CpG sites face away from the histone octamer, the binding affinity was significantly lower. Interestingly, the binding of Delta MBD1 at methylated CpG sites facing away from histone octamers induces conformational changes of nucleosomes, resulting in a more "open" conformation. The biological implication of DNA methylation is thus likely to be synergistically regulated via DNA sequences contents and their nucleosome-positioning patterns based on our in vitro findings.
机译：MBD1的甲基结合结构域是常见的甲基CpG结合基序，与转录抑制有关。理解MBD1与核体DNA的染色的动态至关重要，但MBD1和染色质之间的分子相互作用仍然难以捉摸。在该研究中，我们发现MBD1与核体的结合证明了取决于甲基对核小体上的甲基的位置。具体地，在二元近端区域中的（ME）CpG位点并面向组蛋白八羟寡卷，有利于（ME）CPG位点。在（ME）CPG位点远离组蛋白八寡发物的位置，结合亲和力显着降低。有趣的是，Delta MBD1在远离组蛋白八羟寡卷的甲基化CpG位点的结合诱导核体的构象变化，导致更“开放”的构象。因此，可以通过DNA序列含量及其基于我们的体外发现来协同调节DNA甲基化的生物学意义。

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