12月22日，国际著名杂志Nature在线刊登了研究人员的最新研究成果“DNA-binding factors shape the mouse methylome at distal regulatory regions。”研究人员揭示了低DNA甲基化的调控作用。
DNA的胞嘧啶甲基化是一种在发育和疾病过程中的基因抑制中所涉及的外成修饰。在这项研究中，研究人员在小鼠胚胎干细胞和神经元祖细胞中生成了以碱基对为分辨率的基因组DNA甲基化图。被称为“低甲基化区域”（LMRs，在这些区域中，平均甲基化率约为30%，而不是典型的70%）的特征首次得到了描述。LMRs见于CpG-poor区域，但似乎是结合转录因子的活性调控元素——转录因子结合是生成LMRs所必需的。LMRs在分化过程中是动态的，能预测活性调控区域。（生物谷Bioon.com）
doi:10.1038/nature10716
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DNA-binding factors shape the mouse methylome at distal regulatory regions
Michael B. Stadler,Rabih Murr,Lukas Burger, Robert Ivanek, FlorianLienert,AnneSchöler, Christiane Wirbelauer, Edward J. Oakeley, Dimos Gaidatzis, VijayK.Tiwari&Dirk Schübeler
Methylation of cytosines is an essential epigenetic modification in mammalian genomes, yet the rules that govern methylation patterns remain largely elusive. To gain insights into this process, we generated base-pair-resolution mouse methylomes in stem cells and neuronal progenitors. Advanced quantitative analysis identified low-methylated regions (LMRs) with an average methylation of 30%. These represent CpG-poor distal regulatory regions as evidenced by location, DNase I hypersensitivity, presence of enhancer chromatin marks and enhancer activity in reporter assays. LMRs are occupied by DNA-binding factors and their binding is necessary and sufficient to create LMRs. A comparison of neuronal and stem-cell methylomes confirms this dependency, as cell-type-specific LMRs are occupied by cell-type-specific transcription factors. This study provides methylome references for the mouse and shows that DNA-binding factors locally influence DNA methylation, enabling the identification of active regulatory regions.
