Epigenetic regulation of beta2-adrenergic receptor expression in T(H)1 and T(H)2 cells.
We showed previously that murine naive CD4(+) T cells and T(H)1 cell clones express the beta2-adrenergic receptor (β(2)AR), 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 β(2)AR gene expression, while cells cultured under T(H)2 driving conditions decrease β(2)AR gene expression. Chromatin immunoprecipitation revealed that the increase in β(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 β(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 β(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 β(2)AR gene expression in T(H)1- and T(H)2-driven cells, providing a potential mechanism by which the level of β(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.
Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, OH 43210, USA.
Jaclyn W
JW
McAlees
Laura T
LT
Smith
Robert S
RS
Erbe
David
D
Jarjoura
Nicholas M
NM
Ponzio
Virginia M
VM
Sanders
D000704:Analysis of Variance; D000818:Animals; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D006657:Histones / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism*
D006657:Histones; D012333:RNA, Messenger; D018343:Receptors, Adrenergic, beta-2