Studies using both transgenic mice and transfected mammary epithelial cells
have established that composite response elements containing multiple bind
ing sites for several transcription factors mediate the hormonal and develo
pmental regulation of milk protein gene expression, Activation of signal tr
ansduction pathways by lactogenic hormones and cell-substratum interactions
activate transcription factors and change chromatin structure and milk pro
tein gene expression. The casein promoters have binding sites for signal tr
ansducers and activators of transcription 5, Yin Yang 1, CCAAT/enhancer bin
ding protein, and the glucocorticoid receptor. The whey protein gene promot
ers have binding sites for nuclear factor I, as well as the glucocorticoid
receptor and the signal transducers and activators of transcription 5. The
functional importance of some of these factors in mammary gland development
and milk protein gene expression has been elucidated by studying mice in w
hich some of these factors have been deleted.