The human IL-13 locus in neonatal CD4+ T cells is refractory to the acquisition of a repressive chromatin architecture.
The Th2 cytokine IL-13 is a major effector molecule in human allergic inflammation. Notably, IL-13 expression at birth correlates with subsequent susceptibility to atopic disease. In order to characterize the chromatin-based mechanisms that regulate IL-13 expression in human neonatal CD4(+) T cells, we analyzed patterns of DNase I hypersensitivity and epigenetic modifications within the IL-13 locus in cord blood CD4(+) T cells, naive or differentiated in vitro under Th1- or Th2-polarizing conditions. In naive CD4(+) T cells, hypersensitivity associated with DNA hypomethylation was limited to the distal promoter. Unexpectedly, during both Th1 and Th2 differentiation, the locus was extensively remodeled, as revealed by the formation of numerous HS sites and decreased DNA methylation. Obvious differences in chromatin architecture were limited to the proximal promoter, where strong hypersensitivity, hypomethylation, and permissive histone modifications were found selectively in Th2 cells. In addition to revealing the locations of putative cis-regulatory elements that may be required to control IL-13 expression in neonatal CD4(+) T cells, our results suggest that differential IL-13 expression may depend on the acquisition of a permissive chromatin architecture at the proximal promoter in Th2 cells rather than the formation of locus-wide repressive chromatin in Th1 cells.
Webster
Robin B
RB
Functional Genomics Laboratory, University of Arizona, Tucson, Arizona 85724, USA.
Rodriguez
Yelitza
Y
Klimecki
Walt T
WT
Vercelli
Donata
D
D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D002843:Chromatin / Q000737:chemistry* / Q000378:metabolism; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005312:Fetal Blood / Q000378:metabolism; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006657:Histones / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D018793:Interleukin-13 / Q000235:genetics* / Q000378:metabolism; D008957:Models, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism
D002843:Chromatin; D006657:Histones; D018793:Interleukin-13