Unlocking the Milk Protein Gene Loci During Mammary Gland Development and Differentiation; a Role for Chromatin

Mammary gland development and differentiation occur mostly postnatally. Chromatin organization plays a key role in transcriptional and epigenetic regulation during development and differentiation. Considerable knowledge of the systemic hormones and local growth factors important for development and functional differentiation of the mammary gland exists. However, chromatin’s role in mammary gland development and differentiation has not been defined. We have studied the changes in chromatin organization in the mammary gland before and after functional differentiation at milk protein gene loci, whose gene expression marks functional differentiation of the gland.

We found that within the casein gene cluster and whey acidic protein gene region distal regulatory elements have an open chromatin organization after pubertal development, while proximal promoters gain open-chromatin marks during pregnancy in conjunction with the major induction of their expression. While other milk protein genes already have an open chromatin organization in the mature virgin. In general mammary gland expressed genes and their regulatory elements have a stage- and tissue-specific chromatin organization.

We conclude that a progressive gain of epigenetic marks indicative of open/active chromatin on genes marking functional differentiation accompanies the functional development of the mammary gland. These results support a model in which a poised chromatin organization is established during pubertal development that is then ready to respond to the systemic hormonal signals of pregnancy and lactation to achieve the full functional capacity of the mammary gland.