Combinatorial action of HNF3 and Sp family transcription factors in the activation of the rabbit uteroglobin/CC10 promoter.
It has been reported that respiratory epithelium-specific transcription is mediated by thyroid transcription factor 1 and members of the HNF3/forkhead family of transcription factors. Here, we show that the uteroglobin/Clara cell 10-kDa promoters from rabbit and man are regulated by HNF3alpha and HNF3beta but not by HFH-4 and TTF-1. We have identified two HNF3-responsive elements in the rabbit uteroglobin/CC10 promoter located around 95 and 130 base pairs upstream of the transcriptional start site. Both elements contribute to promoter activity in H441 cells expressing uteroglobin/CC10 and HNF3alpha. Gene transfer experiments into Drosophila Schneider cells that lack many mammalian transcription factor homologs revealed that HNF3alpha and HNF3beta on their own cannot activate the uteroglobin/CC10 promoter. However, HNF3alpha and HNF3beta strongly enhanced Sp1-mediated promoter activation. Synergistic activation by HNF3alpha and Sp1 was absolutely dependent on the integrity of two Sp1 sites located at around -65 and -230. We show further that multiple activation domains of Sp1 are required for cooperativity with HNF3alpha. These studies demonstrate that transcription from the rabbit uteroglobin/CC10 promoter in lung epithelium is controlled by the combinatorial action of the cell-specific factor HNF3alpha and the ubiquitous factor Sp1.
Braun
H
H
Institut für Molekularbiologie und Tumorforschung, Philipps-Universität Marburg, Emil-Mannkopff-Strasse 2, D-35037 Marburg, Germany.
Suske
G
G
D000818:Animals; D001482:Base Composition; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins; D004331:Drosophila melanogaster; D004847:Epithelial Cells / Q000378:metabolism; D051858:Forkhead Transcription Factors; D005786:Gene Expression Regulation; D006801:Humans; D008168:Lung / Q000378:metabolism; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D011817:Rabbits; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D014598:Uteroglobin / Q000096:biosynthesis* / Q000235:genetics
D004268:DNA-Binding Proteins; C477894:FOXI1 protein, human; C106349:FOXJ1 protein, human; D051858:Forkhead Transcription Factors; D011506:Proteins; D011994:Recombinant Proteins; C556389:SCGB1A1 protein, human; D016329:Sp1 Transcription Factor; D015534:Trans-Activators; D014157:Transcription Factors; D014598:Uteroglobin