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Ikaros engages the VPAC1 promoter and recruits HDAC1 in activated HuT78 cells
Author(s) -
Benton Keith D,
Hermann Rebecca J,
Van der Steen Travis,
Failing Jarrett,
Dorsam Glenn P
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.833.2
Subject(s) - downregulation and upregulation , transcription factor , chromatin immunoprecipitation , microbiology and biotechnology , biology , chromatin , chromatin remodeling , promoter , chemistry , gene expression , gene , biochemistry
Proper regulation of the anti‐proliferative G Protein coupled receptor vasoactive intestinal peptide receptor 1 (VPAC1) is important for normal lymphocyte function. VPAC1 mRNA levels are dependent on the activation status of CD4 T cells, as TCR signaling downregulates VPAC1 expression. Ikaros (IK), a transcription factor critical in proper T cell development has been shown to regulate VPAC1 when ectopically overexpressed in NIH‐3T3 cells. Additionally, the VPAC1 locus contains numerous IK binding sites. IK recruits the chromatin remodeling complex NuRD, a HDAC containing multi‐enzyme complex that represses transcription. We hypothesized that IK recruits the NuRD complex upon activation resulting in its downregulation. Binding of IK and HDAC1 to the VPAC1 promoter and gene was queried using chromatin immunoprecipitation. Both were enriched in the VPAC1 locus in an activation dependent manner in the transformed T cell line, HuT 78. This enrichment correlated with the activation induced downregulation of VPAC1. Future studies will overexpress DNA binding, non DNA binding, and alanine/aspartate mutant IK isoforms to determine their effect on IK binding and HDAC1 recruitment. Engagement of the master regulator of lymphopoesis, IK, at the neuropeptide receptor VPAC1 promoter strengthens the neuroimmunomodulation connection at a molecular level. Funding: NIH‐K01 1K01DK064828 and COBRE 2P20RR05566.