Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Laboratory of Epigenetics, Institute of Biomedical Sciences, Fudan University, Shanghai 200032, China.
Mol Cell. 2011 Jul 22;43(2):275-284. doi: 10.1016/j.molcel.2011.07.006.
Histone methylation occurs on both lysine and arginine residues, and its dynamic regulation plays a critical role in chromatin biology. Here we identify the UHRF1 PHD finger (PHD(UHRF1)), an important regulator of DNA CpG methylation, as a histone H3 unmodified arginine 2 (H3R2) recognition modality. This conclusion is based on binding studies and cocrystal structures of PHD(UHRF1) bound to histone H3 peptides, where the guanidinium group of unmodified R2 forms an extensive intermolecular hydrogen bond network, with methylation of H3R2, but not H3K4 or H3K9, disrupting complex formation. We have identified direct target genes of UHRF1 from microarray and ChIP studies. Importantly, we show that UHRF1's ability to repress its direct target gene expression is dependent on PHD(UHRF1) binding to unmodified H3R2, thereby demonstrating the functional importance of this recognition event and supporting the potential for crosstalk between histone arginine methylation and UHRF1 function.
组蛋白甲基化发生在赖氨酸和精氨酸残基上，其动态调控在染色质生物学中起着关键作用。在这里，我们确定 UHRF1 PHD 指（PHD（UHRF1））作为一种组蛋白 H3 未修饰精氨酸 2（H3R2）识别模式，是 DNA CpG 甲基化的重要调节剂。这一结论是基于结合研究和 PHD（UHRF1）与组蛋白 H3 肽结合的共晶结构得出的，其中未修饰的 R2 的胍基形成广泛的分子间氢键网络，H3R2 的甲基化会破坏复合物的形成，但 H3K4 或 H3K9 的甲基化不会。我们已经从微阵列和 ChIP 研究中鉴定出 UHRF1 的直接靶基因。重要的是，我们表明 UHRF1 抑制其直接靶基因表达的能力依赖于 PHD（UHRF1）与未修饰的 H3R2 结合，从而证明了这种识别事件的功能重要性，并支持组蛋白精氨酸甲基化和 UHRF1 功能之间的潜在串扰。
