12月22日,，國(guó)際著名雜志Nature在線(xiàn)刊登了研究人員的最新研究成果“DNA-binding factors shape the mouse methylome at distal regulatory regions。”研究人員揭示了低DNA甲基化的調(diào)控作用,。
DNA的胞嘧啶甲基化是一種在發(fā)育和疾病過(guò)程中的基因抑制中所涉及的外成修飾,。在這項(xiàng)研究中，研究人員在小鼠胚胎干細(xì)胞和神經(jīng)元祖細(xì)胞中生成了以堿基對(duì)為分辨率的基因組DNA甲基化圖,。被稱(chēng)為“低甲基化區(qū)域”（LMRs,，在這些區(qū)域中，平均甲基化率約為30%,，而不是典型的70%）的特征首次得到了描述,。LMRs見(jiàn)于CpG-poor區(qū)域，但似乎是結(jié)合轉(zhuǎn)錄因子的活性調(diào)控元素——轉(zhuǎn)錄因子結(jié)合是生成LMRs所必需的,。LMRs在分化過(guò)程中是動(dòng)態(tài)的，能預(yù)測(cè)活性調(diào)控區(qū)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.
