Epigenetic regulation of beta2-adrenergic receptor expression in TH1 and TH2 cells

We showed previously that murine naive CD4(+) T cells and T(H)1 cell clones express the beta2-adrenergic receptor (beta 2AR), while T(H)2 cell clones do not. We report here that naive CD4(+) T cells that differentiated for 1-5 days under T(H)1 driving conditions increased beta(2)AR gene expression, while cells cultured under T(H)2 driving conditions decrease beta(2)AR gene expression. Chromatin immunoprecipitation revealed that the increase in beta(2)AR gene expression in T(H)1 cells is mediated by an increase in histone 3 (H3) and H4 acetylation, as well as an increase in histone 3 lysine 4 (H3K4) methylation. Conversely, the decrease in beta(2)AR gene expression in T(H)2 cells is mediated by a decrease in H3 and H4 acetylation and a decrease in H3K4 methylation, as well as an increase H3K9 and H3K27 methylation. The histone changes could be detected as early as 3 days of differentiating conditions. Genomic bisulfite sequencing showed that the level of methylated CpG dinucleotides within the promoter of the beta(2)AR gene was increased in T(H)2 cells as compared to naive and T(H)1 cells. Collectively, these results suggest that epigenetic mechanisms mediate maintenance and repression, respectively, of the beta(2)AR gene expression in T(H)1- and T(H)2-driven cells, providing a potential mechanism by which the level of beta(2)AR expression might be modulated pharmacologically within immune cells and other cell types in which the expression profile may change during a disease process. (C) 2010 Elsevier Inc. All rights reserved.