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 vi rus expression primarily to the mammary epithelium. The extreme 5' end of the long terminal repeat contains an enhancer that has been associ ated with tissue-specific expression of the virus. A total of six func tional cis-acting elements have been identified in the enhancer. Altho ugh proteins binding to these elements have been reported, only one ha s been identified; this factor, mp5, is identical or closely related t o the transcription factor AP-2 (Mellentin-Michelotti, J., John, S., P ennie, 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 synerg istically to enhance mouse mammary tumor virus-directed transcription, but only in the presence of glucocorticoid hormone, The F3 element ha s an NF-l-like half-site, but the activity recognizing this element ha s binding characteristics distinct from the NF-1/CTF family as well as the rest of the CCAAT-binding proteins. We conclude that the F3 activ ity represents a new member of the NF-1/CTF family.