Epigenetic mechanisms involved in the induction of the mu opioid receptor gene in Jurkat T cells in response to interleukin-4

Various immunomodulatory effects of opioids are mediated by mu opioid receptors While in resting T lymphocytes their expression is repressed mu opioid receptors are induced by interleukin-4 via the transcription factor STAT6 Here we investigated mechanisms underlying this induction in human Jurkat T cells Although interleukin-4 induced a rapid activation of STAT6 by phosphorylation within few minutes chromatin-immune-precipitation analysis revealed that the binding of STAT6 to its regulatory DNA element on the mu opioid receptor promoter occurs later than h after interleukin-4-stimulation Detectable amounts of the mu opioid receptor mRNA were observed later than 3 h after stimulation Preceding the binding of STAT6 several epigenetic mechanisms were observed that are known to modify the chromatin architecture of a gene Thus we detected by chromatin-immune-precipitation analysis transient association of the mu opioid receptor gene promoter with trimethylated histone H3 at lysine 4 phosphorylated (serine 10) plus acetylated (lysine 14) histone H3 and acetylated histone H4 at lysine 16 In addition binding of the methyl-cytosine-guanine dinucleotide-binding protein MeCP2 to the mu opioid receptor promoter decreased during the interleukin-4 treatment of Jurkat cells Furthermore we detected a transient association of the mu opioid receptor promoter with Brg-1 which is a protein contained in ATP-dependent chromatin remodeling complexes and known to facilitate transcriptional activation of a gene Together these data suggest that epigenetic modifications of the chromatin of the mu opioid receptor gene are involved in the transcriptional activation of the gene in response to interleukin-4 in T cells (C) 2010 Elsevier Ltd All rights reserved