title: Genome-scale profiling reveals a subset of genes regulated by DNA methylation that program somatic T-cell phenotypes in humans.
abstract: 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.
authors.affiliation: Cancer, Disease and Developmental Epigenetics, Murdoch Children's Research Institute, Royal Melbourne Hospital, Parkville, Victoria, Australia.
authors.forename: D
authors.initials: D
authors.lastname: Martino
authors.forename: J
authors.initials: J
authors.lastname: Maksimovic
authors.forename: J-He
authors.initials: JH
authors.lastname: Joo
authors.forename: S L
authors.initials: SL
authors.lastname: Prescott
authors.forename: R
authors.initials: R
authors.lastname: Saffery
mesh_terms: D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D016000:Cluster Analysis; D016207:Cytokines / Q000235:genetics; D019175:DNA Methylation; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008213:Lymphocyte Activation / Q000235:genetics; D010641:Phenotype; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism*
chemical_list: D016207:Cytokines