IL-10 induces DNA binding activity of three STAT proteins (Stat1, Stat3, and Stat5) and their distinct combinatorial assembly in the promoters of selected genes.
Interaction of IL-10 with its receptor leads to the activation of STAT transcription factors. Herein we report the IL-10 dependent simultaneous activation of three STAT transcription factors: Stat1, Stat3, and Stat5. Upon IL-10 treatment multiple Stat proteins become simultaneously activated, and bind to different promoters with equal kinetics but form distinct homo- and heterodimeric transcriptionally active complexes depending on the STAT-consensus elements of a selected gene promoter. Upon IL-10 treatment Stat1, 3, and 5 bind to the GRR of the FcgammaRI gene, activated Stat1 and 3 bind to the SIE sequence of the c-fos promoter and transcriptionally active Stat5 assembles at the PRL-STAT consensus sequence of the beta-casein gene. Thus, functionally relevant STAT dimerization is influenced by the activated cytokine receptor as well as the specific STAT consensus sequence present in a specific gene promoter.
Wehinger
J
J
University of Freiburg Medical Center, Department of Hematology and Oncology, Freiburg, Germany.
Gouilleux
F
F
Groner
B
B
Finke
J
J
Mertelsmann
R
R
Weber-Nordt
R M
RM
D001402:B-Lymphocytes / Q000166:cytology; D002364:Caseins / Q000235:genetics; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D016762:Genes, fos; D006412:Hematopoietic Stem Cells / Q000166:cytology; D016753:Interleukin-10 / Q000494:pharmacology*; D008894:Milk Proteins; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017452:Receptors, IgG / Q000235:genetics; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism*
D002364:Caseins; D004268:DNA-Binding Proteins; D008894:Milk Proteins; D017452:Receptors, IgG; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D016753:Interleukin-10; D004247:DNA