Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, United States of America.
PLoS Genet. 2011 Jun;7(6):e1002154. doi: 10.1371/journal.pgen.1002154. Epub 2011 Jun 23.
Covalent modification of DNA distinguishes cellular identities and is crucial for regulating the pluripotency and differentiation of embryonic stem (ES) cells. The recent demonstration that 5-methylcytosine (5-mC) may be further modified to 5-hydroxymethylcytosine (5-hmC) in ES cells has revealed a novel regulatory paradigm to modulate the epigenetic landscape of pluripotency. To understand the role of 5-hmC in the epigenomic landscape of pluripotent cells, here we profile the genome-wide 5-hmC distribution and correlate it with the genomic profiles of 11 diverse histone modifications and six transcription factors in human ES cells. By integrating genomic 5-hmC signals with maps of histone enrichment, we link particular pluripotency-associated chromatin contexts with 5-hmC. Intriguingly, through additional correlations with defined chromatin signatures at promoter and enhancer subtypes, we show distinct enrichment of 5-hmC at enhancers marked with H3K4me1 and H3K27ac. These results suggest potential role(s) for 5-hmC in the regulation of specific promoters and enhancers. In addition, our results provide a detailed epigenomic map of 5-hmC from which to pursue future functional studies on the diverse regulatory roles associated with 5-hmC.
DNA 的共价修饰区分了细胞身份，对于调控胚胎干细胞（ES 细胞）的多能性和分化至关重要。最近的研究表明，5-甲基胞嘧啶（5-mC）在 ES 细胞中可能进一步修饰为 5-羟甲基胞嘧啶（5-hmC），这揭示了一种新的调节多能性表观基因组景观的调控模式。为了了解 5-hmC 在多能细胞表观基因组景观中的作用，我们在这里绘制了人类 ES 细胞中全基因组 5-hmC 分布图谱，并将其与 11 种不同的组蛋白修饰和 6 种转录因子的基因组图谱进行了关联。通过将基因组 5-hmC 信号与组蛋白富集图谱进行整合，我们将特定的与多能性相关的染色质环境与 5-hmC 联系起来。有趣的是，通过与启动子和增强子亚型的定义染色质特征的进一步关联，我们发现 H3K4me1 和 H3K27ac 标记的增强子中 5-hmC 明显富集。这些结果表明 5-hmC 在调控特定启动子和增强子方面可能具有潜在作用。此外，我们的研究结果提供了一个详细的 5-hmC 表观基因组图谱，可用于研究与 5-hmC 相关的多种调控作用的功能。
