c-Rel is a selective activator of a novel IL-4/CD40 responsive element in the human Ig gamma4 germline promoter

Molecular Immunology
Alessandra Agresti, D Vercelli

Abstract

Induction of isotype switching to a specific C(H) gene correlates with the transcriptional activation of the same gene in germline (GL) configuration. Expression of correctly spliced GL transcripts is necessary to target a switch region for recombination. In human B cells, the IgE and IgG4 isotypes are both induced by IL-4 through sequential switching, but are functionally antagonistic because IgG4 appears to have IgE-blocking activity. In order to understand the molecular mechanisms that regulate IgG4 production, we undertook a systematic analysis of the gamma4 GL promoter. A HindIII/NaeI region (-421/+474) highly conserved in the human gamma locus mediated the synergistic activation of a reporter gene in response to IL-4 and CD40 cross-linking. STAT6 binding to the proximal gamma4 GL promoter was essential for both IL-4-induced activation and CD40-dependent enhancement of transcription. Of note, a 45bp region (-76/-32) centered around the STAT6 binding motif drove robust synergistic activation of a heterologous fos promoter upon stimulation with IL-4 and CD40 cross-linking. This finding suggested that the (-76/-32) region may contain a novel IL-4/CD40 responsive element (RE). Electrophoretic mobility shift assays (EMSA) analy...Continue Reading

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Citations

Mar 29, 2011·Immunologic Research·Shreevrat Goenka, Mark H Kaplan
Sep 24, 2004·The Journal of Experimental Medicine·Yuan Xiao ZhuA Keith Stewart
May 11, 2010·Cold Spring Harbor Perspectives in Biology·Steve Gerondakis, Ulrich Siebenlist
Feb 20, 2016·Current Allergy and Asthma Reports·Louisa K James, Stephen J Till
Apr 28, 2004·Journal of Dental Research·E GemmellG J Seymour
Jul 25, 2003·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Hsiou-Chi Liou, Constance Y Hsia
Mar 5, 2020·Cellular and Molecular Life Sciences : CMLS·Shrikanth C Basavarajappa, Parameswaran Ramakrishnan
Feb 3, 2004·Oncogene·Thomas D GilmoreDaniel T Starczynowski
Jul 6, 2021·Frontiers in Immunology·C ZografouP Stathopoulos

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