A T-cell-specific CD154 transcriptional enhancer located just upstream of the promoter.

Genes and Immunity
M BrunnerRandy Q Cron

Abstract

CD154 (CD40-ligand) is a critical immune regulator. CD154 expression is tightly regulated and largely restricted to activated CD4 T cells. Using DNase I hypersensitivity site (HSS) mapping, we identified two novel HSS mapping to the human CD154 promoter element and just upstream. Both HSS were activation independent and CD4 T-cell specific. Approximately 350 bp of DNA sequence flanking the upstream HSS site was highly conserved between mouse and man, and was rich in binding sites for GATA and NFAT proteins. Gel shift and chromatin immunoprecipitation assays demonstrated both NFAT1 and the Th2 factor, GATA-3, bound this enhancer element in vitro and in vivo, respectively. A PstI/XbaI 345 bp fragment of this region acted as a transcriptional enhancer of the CD154 promoter in primary human CD4 T cells. Overexpression of repressor of GATA and a dominant negative GATA-3 protein independently inhibited transcription, whereas overexpression of wild-type GATA-3 enhanced transcriptional activity, by this element in primary CD4 T cells. Moreover, more interleukin-4-producing CD4 T cells expressed CD154 following activation than interferon-gamma-producing CD4 T cells. Thus, we identified a novel T-cell-specific, GATA-3 responsive, CD154 t...Continue Reading

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Citations

Jul 7, 2012·Cell Communication and Signaling : CCS·Edgar SerflingFriederike Berberich-Siebelt
Aug 27, 2014·The Journal of Clinical Investigation·Patrick J ShawStefan Feske
Jul 3, 2009·European Journal of Immunology·Stefano VavassoriLori R Covey
Dec 15, 2010·PloS One·Carlos RiverosUNKNOWN ANZgene Multiple Sclerosis Genetics Consortium
Nov 26, 2010·Biochemical and Biophysical Research Communications·Heni SusilowatiYoichiro Miyake
Jul 4, 2018·PloS One·Emily MacLean ScottLisa Cameron

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