| A transcriptionally permissive epigenetic landscape at the vasoactive intestinal peptide receptor-1 promoter suggests a euchromatin nuclear position in murine CD4 T cells. | |
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MedLine Citation:
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PMID: 19729043 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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K D Benton; R J Hermann; E E Vomhof-DeKrey; J S Haring; T Van der Steen; J Smith; S Dovat; G P Dorsam |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2009-09-01 |
Journal Detail:
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Title: Regulatory peptides Volume: 158 ISSN: 1873-1686 ISO Abbreviation: Regul. Pept. Publication Date: 2009 Nov |
Date Detail:
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Created Date: 2009-10-13 Completed Date: 2010-01-25 Revised Date: 2011-06-06 |
Medline Journal Info:
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Nlm Unique ID: 8100479 Medline TA: Regul Pept Country: Netherlands |
Other Details:
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Languages: eng Pagination: 68-76 Citation Subset: IM |
Affiliation:
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Department of Chemistry and Molecular Biology, North Dakota State University, Fargo, ND 58108, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acetylation Animals Base Sequence CD4-Positive T-Lymphocytes / metabolism* Cell Nucleus / metabolism* Chromatin Immunoprecipitation DNA Primers Down-Regulation Epigenesis, Genetic* Euchromatin / metabolism* Methylation Mice Polymerase Chain Reaction RNA, Messenger / genetics Receptors, Vasoactive Intestinal Polypeptide, Type I / genetics* Signal Transduction Transcription, Genetic |
| Grant Support | |
ID/Acronym/Agency:
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1KO1DK064828/DK/NIDDK NIH HHS; 2P20RR015566/RR/NCRR NIH HHS; K01 DK064828-05/DK/NIDDK NIH HHS; P20RR016741/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/DNA Primers; 0/Euchromatin; 0/RNA, Messenger; 0/Receptors, Vasoactive Intestinal Polypeptide, Type I |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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