A nuclear factor 1 binding site mediates the transcriptional activation of a type I collagen promoter by transforming growth factor-beta.
Transforming growth factor-beta (TGF-beta) increases the steady-state RNA levels of several fibroblast extracellular matrix proteins. Using DNA transfection, we show that TGF-beta stimulates the activity of the mouse alpha 2(l) collagen promoter 5- to 10-fold in mouse NIH 3T3 and rat osteosarcoma cells. Deletion analysis indicates that a segment of this promoter between -350 and -300, overlapping a nuclear factor 1 (NF1) binding site, is needed for TGF-beta stimulation. A 3 bp substitution mutation abolishing NF1 binding to this site inhibits TGF-beta activation. Insertion of this NF1 binding site 5' to the SV40 early promoter makes the promoter TGF-beta inducible, but the 3 bp substitution does not. Similarly, when the NF1 binding site at the replication origin of adenovirus 2 and 5 is inserted 5' to the SV40 promoter, the promoter responds to TGF-beta. Therefore an NF1 binding site mediates the transcriptional activation of the mouse alpha 2(l) collagen promoter by TGF-beta.
Rossi
P
P
Laboratory of Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892.
Karsenty
G
G
Roberts
A B
AB
Roche
N S
NS
Sporn
M B
MB
de Crombrugghe
B
B
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D022762:CCAAT-Enhancer-Binding Proteins; D003094:Collagen / Q000096:biosynthesis / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D006133:Growth Substances / Q000494:pharmacology*; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D051839:NFI Transcription Factors; D009687:Nuclear Proteins; D010455:Peptides / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D051381:Rats; D013539:Simian virus 40 / Q000235:genetics; D014157:Transcription Factors; D014162:Transfection; D015291:Transforming Growth Factors; D051840:Y-Box-Binding Protein 1
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D006133:Growth Substances; D051839:NFI Transcription Factors; D009687:Nuclear Proteins; D010455:Peptides; D014157:Transcription Factors; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human; D015291:Transforming Growth Factors; D003094:Collagen