Repression participates in mammary tissue-specific activation of the caprine beta-lactoglobulin promoter

Activation of the beta-lactoglobulin (BLG) gene promoter is restricted to overtly differentiated mammary tissue. To understand the mechanism underlying such tissue-specificity, activity of the caprine BLG promoter was analyzed comparatively in cultured mammary HC11 cells and non-mammary HeLa and CV-1 cells. The BLG promoter flanked by the 5'-regulatory sequence below -205 was strongly activated in the cells, regardless of the cell type. In non-mammary HeLa and CV-1 cells, this activation was repressed completely by the upper regulatory sequence. Weak repression was also observed in mammary HC11 cells kept non-confluent. As the mammary HC11 cells grew confluent and maintained the stabilized state, however, repression by the upper regulatory sequence was switched to activation. The repressive upstream flanking sequence was strongly recognized by the binding factors in non-mammary HeLa and CV-1 cells in an in vitro binding assay. Binding intensity and competition strength of the upstream regulatory regions were in a close correlation to their transcriptional repression activities in the cultured cells. The results suggest that the restricted activation of the caprine BLG promoter in differentiated mammary tissue is guaranteed by repression in non-mammary and undifferentiated mammary cells.