Characterization of an NF-1/CTF family member as a functional activator of the mouse mammary tumor virus long terminal repeat 5' enhancer.
The long terminal repeat of the mouse mammary tumor virus restricts virus expression primarily to the mammary epithelium. The extreme 5' end of the long terminal repeat contains an enhancer that has been associated with tissue-specific expression of the virus. A total of six functional cis-acting elements have been identified in the enhancer. Although proteins binding to these elements have been reported, only one has been identified; this factor, mp5, is identical or closely related to the transcription factor AP-2 (Mellentin-Michelotti, J., John, S., Pennie, W. D., Williams, T., and Hager, G. L. (1994) J. Biol. Chem. 269, 31983-31990). The other factors are hitherto unidentified and poorly described. We report here the characterization of another of the six elements, previously referred to as the F3 site (Mink, S., Hartig, E., Jennewein, P., Doppler, W., and Cato, A. C. (1992) Mol. Cell Biol. 12, 4906-4918). We show that the F3 binding activity and AP-2 act synergistically to enhance mouse mammary tumor virus-directed transcription, but only in the presence of glucocorticoid hormone. The F3 element has an NF-1-like half-site, but the activity recognizing this element has binding characteristics distinct from the NF-1/CTF family as well as the rest of the CCAAT-binding proteins. We conclude that the F3 activity represents a new member of the NF-1/CTF family.
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Laboratory of Receptor Biology and Gene Expression, NCI, National Institutes of Health, Bethesda, Maryland 20892-5055, USA. hagerg@dce41.nci.nih.gov
John
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Fragoso
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Michelotti
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Hager
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D000818:Animals; D001483:Base Sequence; D022762:CCAAT-Enhancer-Binding Proteins; D018983:DNA Footprinting; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D051839:NFI Transcription Factors; D012091:Repetitive Sequences, Nucleic Acid; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D014162:Transfection
D022762:CCAAT-Enhancer-Binding Proteins; C077305:CTF-1 transcription factor; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D051839:NFI Transcription Factors; D050656:Transcription Factor AP-2; D014157:Transcription Factors