A transcriptionally permissive epigenetic landscape at the vasoactive intestinal peptide receptor-1 promoter suggests a euchromatin nuclear position in murine CD4 T cells

• Published in: Regulatory peptides Vol. 158; no. 1; pp. 68 - 76
• Main Authors: Benton, K.D., Hermann, R.J., Vomhof-DeKrey, E.E., Haring, J.S., Van der Steen, T., Smith, J., Dovat, S., Dorsam, G.P.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 27.11.2009
• Subjects: Acetylation; Animals; Base Sequence; CD4-Positive T-Lymphocytes - metabolism; Cell Nucleus - metabolism; Chromatin Immunoprecipitation; DNA Primers; Down-Regulation; Epigenesis, Genetic; Euchromatin; Euchromatin - metabolism; Histone acetylation; Histone methylation; Methylation; Mice; Neuropeptides; Polymerase Chain Reaction; Receptors, Vasoactive Intestinal Polypeptide, Type I - genetics; RNA, Messenger - genetics; Signal Transduction; TCR signaling; Transcription, Genetic; VPAC1; TCR signaling; Neuropeptides; Histone acetylation; VPAC1; Histone methylation; Euchromatin
• ISSN: 0167-0115; 1873-1686
• DOI: 10.1016/j.regpep.2009.08.010

T cells express receptors for neuropeptides that mediate immunological activities. Vasoactive intestinal peptide receptor-1 (VPAC1), the prototypical group II G protein coupled receptor, binds two neuropeptides with high-affinity, called vasoactive intestinal peptide and pituitary adenylate cyclase activating polypeptide. During T cell signaling, VPAC1 mRNA expression levels are significantly downregulated through a Src kinase dependent mechanism, thus altering the sensitivity for these neuropeptides during an immune reaction. Presently, it is unknown whether the mechanism that regulates VPAC1 during T cell signaling involves epigenetic changes. Therefore, we hypothesized that the epigenetic landscape consisting of diacetylation at H3K9/14 and trimethylation at H3K4, two transcriptionally permissive histone modifications, would parallel VPAC1 expression showing high enrichment in untreated T cells, but lower enrichment in α-CD3 treated T cells. To this end, quantitative chromatin immunoprecipitation (ChIP) analysis of H3K9/14ac and H3K4me3 was conducted using purified CD4 + T cells, with CD45R + B cells as a negative control. Our data revealed that these histone modifications at the VPAC1 promoter did indeed parallel its mRNA levels between T and B lymphocytes, but did not decrease during T cell signaling. Collectively, these data strongly imply a euchromatin nuclear position for the VPAC1 locus irrespective of the activation status of T cells.