Dissecting the dynamic changes of 5-hydroxymethylcytosine in T cell development and differentiation [CMS-Seq]

The discovery of TET proteins, enzymes that oxidize 5-methylcytosine (5mC) in DNA, has revealed novel mechanisms for the regulation of DNA methylation. We have mapped 5-hydroxymethylcytosine (5hmC) at different stages of T cell development in the thymus and T cell differentiation in the periphery. We show that 5hmC is enriched in the gene body of highly expressed genes at all developmental stages, and that its presence correlates positively with gene expression. Further emphasizing the connection with gene expression, we find that 5hmC is enriched in active thymus-specific enhancers, and that genes encoding key transcriptional regulators display high intragenic 5hmC levels in precursor cells at those developmental stages where they exert a positive effect. Our data constitute a valuable resource that will facilitate detailed analysis of the role of 5hmC in T cell development and differentiation. Study the distribution of 5hmC in 7 T cell subsets at sequential steps of development, differentiation and specification

TET蛋白（TET proteins）作为可催化DNA中5-甲基胞嘧啶（5-methylcytosine, 5mC）氧化反应的酶类，其发现揭示了DNA甲基化调控的全新机制。本研究针对胸腺内T细胞发育及外周T细胞分化的不同阶段，完成了5-羟甲基胞嘧啶（5-hydroxymethylcytosine, 5hmC）的图谱绘制。研究表明，在所有发育阶段中，5hmC均富集于高表达基因的基因体区域，且其水平与基因表达呈显著正相关。为进一步明确5hmC与基因表达的关联，我们发现：5hmC富集于活跃的胸腺特异性增强子区域；在关键转录调节因子发挥正向调控作用的发育阶段，其对应的前体细胞内，编码这类因子的基因呈现出较高的基因内5hmC水平。本研究数据属于宝贵的科研资源，将为学界深入解析5hmC在T细胞发育与分化过程中的功能提供重要支撑。本研究同时探究了7种T细胞亚群在发育、分化及细胞特化的连续进程中的5hmC分布特征。