DEVELOPMENTAL AND ENVIRONMENTAL-REGULATION OF A MAMMARY GLAND-SPECIFIC NUCLEAR FACTOR ESSENTIAL FOR TRANSCRIPTION OF THE GENE ENCODING BETA-CASEIN

During the lactation period, mammary epithelial cells secrete large am ounts of milk proteins. The coordinate regulation of milk protein expr ession is effected by the lactogenic hormones. We have investigated th e activity of a mammary gland-specific transcription factor (MGF), whi ch mediates hormonal influences at the level of a milk protein gene pr omoter. MGF-binding sites are present in the promoters of the most abu ndantly expressed milk protein genes. Mutation of the MGF-binding site in the beta-casein gene promoter completely abolishes responsiveness of the promoter to lactogenic hormones in cultured mammary epithelial cells. MGF activity is closely controlled in vivo. High MGF levels wer e found in mouse mammary gland nuclear extracts toward the end of preg nancy and during lactation. Withdrawal of suckling pups from their mot hers during the lactation period caused a strong and rapid decrease of MGF activity. Readdition of pups to their mothers restored maximal MG F levels within 4 hr. We investigated MGF phosphorylation as a possibl e posttranslational modification responsible for regulation of the DNA -binding activity of MGF. Treatment of nuclear extracts from lactating mammary glands with potato acid phosphatase abolished MGF-binding act ivity. Casein kinase II phosphorylation of nuclear extracts from anima ls withdrawn from their pups for 24 hr enhanced MGF-binding activity. These results suggest that the reversible activation of MGF by sucklin g and withdrawal might be mediated by the action of kinases and phosph atases.