Cooperative interactions of AP-1 and basic helix-loop-helix transcription factors regulate T1 gene expression.
The T1 gene is a murine, delayed early serum-responsive gene that encodes glycoproteins of the interleukin-1 receptor (IL-1R) family. Transcription of the T1 gene leads to production of two mRNAs that encode a transmembrane protein, which is highly similar to the type-1 IL-1R, and a secreted protein, which consists solely of the extracellular part. Fibroblasts, in contrast to mast cells, express predominantly the shorter form of the protein, and several mitogens cause strong, transient induction of the T1 gene in these cells. Here we describe the identification of a 148 bp enhancer element that is positioned 3.6 kb upstream of the transcription initiation site. A TPA-responsive element (TRE) and three identical E-boxes are located within this sequence. Introduced point mutations confirmed the necessity of these sites for full T1 promoter activity. The TRE and the distal E-box are absolutely indispensable for promoter function, whereas the two proximal E-boxes contribute less to promoter strength. In vitro the three E-boxes are bound by different protein complexes.
Kessler
R
R
Department of Pathology, University Hospital, Zürich, Switzerland.
Laursen
N B
NB
Trüb
T
T
Kalousek
M B
MB
Klemenz
R
R
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D016193:G1 Phase / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D018257:Helix-Loop-Helix Motifs / Q000235:genetics* / Q000502:physiology; D000072179:Interleukin-1 Receptor-Like 1 Protein; D008565:Membrane Proteins; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011506:Proteins / Q000187:drug effects / Q000235:genetics*; D018123:Receptors, Interleukin; D011993:Recombinant Fusion Proteins / Q000502:physiology; D016192:Resting Phase, Cell Cycle / Q000235:genetics; D018808:Transcription Factor AP-1 / Q000378:metabolism* / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D014407:Tumor Cells, Cultured
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D000072179:Interleukin-1 Receptor-Like 1 Protein; D008565:Membrane Proteins; D011506:Proteins; D018123:Receptors, Interleukin; D011993:Recombinant Fusion Proteins; D018808:Transcription Factor AP-1; D014157:Transcription Factors; C486189:Il1rl1 protein, mouse