Modulation of basal expression of the human alpha1(I) procollagen gene (COL1A1) by tandem NF-1/Sp1 promoter elements in normal human dermal fibroblasts.
We previously demonstrated that a segment of the human alpha1 type I procollagen gene (COL1A1) promoter encompassing nt -174 to -84 is responsible for the highest transcriptional activity in collagen producing cells in vitro. Here, we identified two almost identical tandem NF-1/Sp1 binding sites located between nt -129 to -107 (distal element) and nt -104 to -77 (proximal element) that are responsible for the basal regulation of COL1A1 transcription in normal human dermal fibroblasts. Transient transfection studies revealed that 85% of the basal COL1A1 promoter activity resides within the distal element; however, site-directed mutagenesis within the CCAAT motif in the proximal element resulted in a 98% decrease of the COL1A1 promoter activity. We conclude that each of the NF-1/Sp1 tandem binding sites has a different function. The distal element drives the transcriptional activity of the COL1A1 promoter but is not sufficient for its basal expression, whereas the NF-1 binding site in the proximal element is essential for in vitro COL1A1 gene transcription.
Artlett
C M
CM
Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Chen
S J
SJ
Varga
J
J
Jimenez
S A
SA
D001483:Base Sequence; D001665:Binding Sites; D001667:Binding, Competitive; D022762:CCAAT-Enhancer-Binding Proteins; D018983:DNA Footprinting; D004268:DNA-Binding Proteins / Q000235:genetics*; D003850:Deoxyribonuclease I; D005347:Fibroblasts; D005786:Gene Expression Regulation; D006801:Humans; D008969:Molecular Sequence Data; D051839:NFI Transcription Factors; D009687:Nuclear Proteins; D011347:Procollagen / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012867:Skin / Q000166:cytology; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D051840:Y-Box-Binding Protein 1
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D051839:NFI Transcription Factors; D009687:Nuclear Proteins; D011347:Procollagen; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human; D003850:Deoxyribonuclease I