IL-10 gene expression is controlled by the transcription factors Sp1 and Sp3.
IL-10 is an 18-kDa cytokine with a key role in homeostatic control of inflammatory and immune responses. We have investigated how transcription of the IL-10 gene is regulated, so as to be able to understand the circumstances of IL-10 expression in both health and disease. In the mouse, IL-10 gene expression is regulated by a TATA-type promoter with a critical cis-acting element containing GGA repeats located at -89 to -77. Its complementary sequence is similar to the cis-acting elements (TCC repeats) in the promoters of genes encoding epidermal growth factor receptor and CD58. All these elements comprise a common CCTCCT sequence with less conserved C + T-rich sequences. Eliminating this CCTCCT sequence results in a marked reduction in promoter activity, suggesting a necessary role in IL-10 gene expression. Despite its dissimilarity to the G + C-rich Sp1 consensus sequence (GC box), Sp1 and Sp3 transcription factors could be shown to bind to this motif. The requirement for Sp1 and Sp3 in transcription of IL-10 was confirmed using Drosophila SL2 cells, which lack endogenous Sp factors. These results suggest that the transcription of IL-10 is positively regulated by both Sp1 and Sp3.
Tone
M
M
Sir William Dunn School of Pathology, University of Oxford, United Kingdom. mtone@molbiol.ox.ac.uk
Powell
M J
MJ
Tone
Y
Y
Thompson
S A
SA
Waldmann
H
H
D020121:5' Untranslated Regions / Q000276:immunology; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D005786:Gene Expression Regulation / Q000276:immunology*; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000276:immunology; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D012045:Regulatory Sequences, Nucleic Acid / Q000276:immunology; D016329:Sp1 Transcription Factor / Q000378:metabolism / Q000502:physiology*; D051705:Sp3 Transcription Factor; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*
D020121:5' Untranslated Regions; D004268:DNA-Binding Proteins; D016329:Sp1 Transcription Factor; C497122:Sp3 protein, mouse; D014157:Transcription Factors; D016753:Interleukin-10; D051705:Sp3 Transcription Factor