Cancer, Disease and Developmental Epigenetics, Murdoch Children's Research Institute, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Genes Immun. 2012 Jul;13(5):388-98. doi: 10.1038/gene.2012.7. Epub 2012 Apr 12.
The aim of this study was to investigate the dynamics and relationship between DNA methylation and gene expression during early T-cell development. Mononuclear cells were collected at birth and at 12 months from 60 infants and were either activated with anti-CD3 for 24 h or cultured in media alone, and the CD4+ T-cell subset purified. DNA and RNA were co-harvested and DNA methylation was measured in 450 000 CpG sites in parallel with expression measurements taken from 25 000 genes. In unstimulated cells, we found that a subset of 1188 differentially methylated loci were associated with a change in expression in 599 genes (adjusted P value<0.01, β-fold >0.1). These genes were enriched in reprogramming regions of the genome known to control pluripotency. In contrast, over 630 genes were induced following low-level T-cell activation, but this was not associated with any significant change in DNA methylation. We conclude that DNA methylation is dynamic during early T-cell development, and has a role in the consolidation of T-cell-specific gene expression. During the early phase of clonal expansion, DNA methylation is stable and therefore appears to be of limited importance in short-term T-cell responsiveness.
本研究旨在探究早期 T 细胞发育过程中 DNA 甲基化和基因表达的动态变化及其关系。从 60 名婴儿出生时和 12 个月时采集单核细胞，用抗 CD3 激活 24 小时或单独在培养基中培养，并纯化 CD4+T 细胞亚群。同时在 450000 个 CpG 位点测量 DNA 甲基化，并对 25000 个基因的表达进行测量。在未受刺激的细胞中，我们发现 1188 个差异甲基化基因座中有一部分与 599 个基因的表达变化相关（调整后的 P 值<0.01，β倍数>0.1）。这些基因富集在已知控制多能性的基因组重编程区域。相比之下，低水平 T 细胞激活后诱导了超过 630 个基因，但这与 DNA 甲基化的任何显著变化无关。我们得出结论，DNA 甲基化在早期 T 细胞发育过程中是动态的，在 T 细胞特异性基因表达的巩固中发挥作用。在克隆扩增的早期阶段，DNA 甲基化是稳定的，因此在短期 T 细胞反应中似乎不重要。
