Identification of a distal tandem STAT6 element within the CCL17 locus.
The CC chemokine ligand CCL17 is one of the major chemo-attractants for T(H)2 cells. Interleukin-4-induced activation of CCL17 expression was recently demonstrated to result from two STAT6 motifs in the proximal promoter. Here we provide evidence that a distal tandem STAT6 element further elevates expression from the CCL17 locus approximately twofold. This is demonstrated by reporter gene assays using different fragments of the CCL17 promoter and the region 2.5 kb upstream from the transcriptional start site. By electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation experiments, we show that STAT6 binds to the motifs in vitro and in vivo, respectively. Insertion of nucleotide exchanges into the STAT6 core motifs results in diminished promoter activation and abrogated STAT6 binding, as demonstrated by reporter gene and EMSA studies. Collectively these data reveal an additional element involved in the regulation of CCL17 expression.
Maier
Elisabeth
E
Department of Molecular Biology, University of Salzburg, Salzburg, Austria.
Wirnsberger
Gerald
G
Horejs-Hoeck
Jutta
J
Duschl
Albert
A
Hebenstreit
Daniel
D
D001483:Base Sequence; D002478:Cells, Cultured; D054414:Chemokine CCL17 / Q000235:genetics* / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D015847:Interleukin-4 / Q000276:immunology*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D050800:STAT6 Transcription Factor / Q000235:genetics* / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D024363:Transcription Initiation Site
C106230:CCL17 protein, human; D054414:Chemokine CCL17; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D015847:Interleukin-4