A mouse mammary tumor virus promoter element near the transcription initiation site.
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abstract
Transcription from the promoter of mouse mammary tumor virus is subject to both positive and negative control by cellular factors, and proviral promoter elements that mediate a basal level of transcription must in some way respond to these cellular regulatory signals. Several such elements, including a TATA box, a region containing three octamer-related sequences, and a binding site for nuclear factor 1, have been previously defined. Additional promoter mutations have allowed a fourth basal promoter element to be identified near the transcription initiation site between +2 and +10. Sequence alterations within this element affect transcription both in vivo and in vitro. Gel electrophoresis mobility shift and DNase I footprinting assays define a nuclear protein, termed initiation site-binding protein, that specifically recognizes this region of the promoter. Optimal levels of transcription from the mouse mammary tumor virus promoter require initiation site-binding protein, as demonstrated by a correlation between protein affinity and transcriptional activity and by specific inhibition of transcription in vitro by an oligonucleotide capable of titrating the protein from transcriptionally active fractions.