title: A transcriptionally permissive epigenetic landscape at the vasoactive intestinal peptide receptor-1 promoter suggests a euchromatin nuclear position in murine CD4 T cells.
abstract: 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 alpha-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.
authors.affiliation: Department of Chemistry and Molecular Biology, North Dakota State University, Fargo, ND 58108, USA.
authors.forename: K D
authors.initials: KD
authors.lastname: Benton
authors.forename: R J
authors.initials: RJ
authors.lastname: Hermann
authors.forename: E E
authors.initials: EE
authors.lastname: Vomhof-DeKrey
authors.forename: J S
authors.initials: JS
authors.lastname: Haring
authors.forename: T
authors.initials: T
authors.lastname: Van der Steen
authors.forename: J
authors.initials: J
authors.lastname: Smith
authors.forename: S
authors.initials: S
authors.lastname: Dovat
authors.forename: G P
authors.initials: GP
authors.lastname: Dorsam
mesh_terms: D000107:Acetylation; D000818:Animals; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D017931:DNA Primers; D015536:Down-Regulation; D044127:Epigenesis, Genetic; D022041:Euchromatin / Q000378:metabolism*; D008745:Methylation; D051379:Mice; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I / Q000235:genetics*; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D017931:DNA Primers; D022041:Euchromatin; D012333:RNA, Messenger; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I