1] Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK [2] Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
Department of Proteomics, The Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3B, DK-2200 Copenhagen, Denmark.
Nature. 2014 Jan 23;505(7484):564-8. doi: 10.1038/nature12819. Epub 2013 Dec 18.
Nucleosomes are decorated with numerous post-translational modifications capable of influencing many DNA processes. Here we describe a new class of histone modification, methylation of glutamine, occurring on yeast histone H2A at position 105 (Q105) and human H2A at Q104. We identify Nop1 as the methyltransferase in yeast and demonstrate that fibrillarin is the orthologue enzyme in human cells. Glutamine methylation of H2A is restricted to the nucleolus. Global analysis in yeast, using an H2AQ105me-specific antibody, shows that this modification is exclusively enriched over the 35S ribosomal DNA transcriptional unit. We show that the Q105 residue is part of the binding site for the histone chaperone FACT (facilitator of chromatin transcription) complex. Methylation of Q105 or its substitution to alanine disrupts binding to FACT in vitro. A yeast strain mutated at Q105 shows reduced histone incorporation and increased transcription at the ribosomal DNA locus. These features are phenocopied by mutations in FACT complex components. Together these data identify glutamine methylation of H2A as the first histone epigenetic mark dedicated to a specific RNA polymerase and define its function as a regulator of FACT interaction with nucleosomes.
核小体上有许多翻译后修饰，这些修饰能够影响许多 DNA 过程。在这里，我们描述了一种新的组蛋白修饰类型，即位于酵母组蛋白 H2A 的第 105 位（Q105）和人类 H2A 的第 104 位的谷氨酰胺甲基化。我们鉴定出 Nop1 是酵母中的甲基转移酶，并证明在人类细胞中，fibrillarin 是其同源酶。H2A 的谷氨酰胺甲基化仅限于核仁。在酵母中的全局分析中，我们使用针对 H2AQ105me 的特异性抗体，发现该修饰仅在 35S 核糖体 DNA 转录单位上富集。我们表明，Q105 残基是组蛋白伴侣 FACT（染色质转录辅助因子）复合物结合位点的一部分。Q105 残基的甲基化或其突变为丙氨酸会破坏其与 FACT 的体外结合。在 Q105 突变的酵母菌株中，核糖体 DNA 基因座的组蛋白掺入减少，转录增加。这些特征可通过 FACT 复合物成分的突变来模拟。这些数据共同表明，H2A 的谷氨酰胺甲基化是第一个专门针对特定 RNA 聚合酶的组蛋白表观遗传标记，并定义了其作为 FACT 与核小体相互作用的调节剂的功能。
