HORMONAL-REGULATION OF TRANSCRIPTION FACTOR ACTIVITY IN MAMMARY EPITHELIAL-CELLS

The multihormonal control of milk protein gene transcription in mammar y epithelial cells has been investigated. Although the hormones regula ting milk protein gene expression are known, the interaction of the si gnal transduction pathways of steroid (glucocorticoids) and peptide (i nsulin and prolactin) hormones remains undefined in molecular terms. T hese signals converge on the level of nuclear factors binding to regul atory elements in the beta-casein gene promoter. The promoter has a mo dular architecture and is composed of positive and negative response e lements. Nuclear transcription factors which bind to these elements ha ve been identified. The mammary gland factor, MGF, is an essential med iator of lactogenic hormone action and is itself positively regulated in its DNA binding activity. It binds to the promoter region between p ositions -80 to -100. MGF counteracts a repressor element, constituted by two components, whichis located adjacent to the MGF binding site a t positions -100 to -150. The transcription factor YY1 binds to the pr oximal half of the repressor element which overlaps with the MGF bindi ng site. Specific single-stranded DNA binding proteins contribute to t he negative regulation of the promoter by interacting with sequence el ements between -160 and -190. DNA binding of these proteins is negativ ely regulated by the lactogenic hormones.