Location: Children's Nutrition Research CenterTitle: The epigenetic landscape of mammary gland development and functional differentiation Author
Submitted to: Journal of Mammary Gland Biology and Neoplasia
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/21/2010
Publication Date: 2/17/2010
Citation: Rijnkels, M., Kabotyanski, E., Montazer-Torbati, M.B., Beauvis, C.H., Vassetzky, Y., Rosen, J.M., Devinoy, E. 2010. The epigenetic landscape of mammary gland development and functional differentiation. Journal of Mammary Gland Biology and Neoplasia. 15:85-100. Interpretive Summary: The mammary gland develops mostly after birth. The way DNA is packaged in the cell nucleus contributes to its epigenetic state (how gene expression is altered during development). We know very little about how epigenetic regulation and the packaging of DNA contribute to mammary gland development. The current data indicate that epigenetic regulation is involved in mammary gland development, lactation, and disease. New tools to study epigenetics will facilitate further studies aimed at understanding how hormonal pathways intersect with epigenetic control in development, which is important to further understand early mammary gland development and disease development.
Technical Abstract: Most of the development and functional differentiation in the mammary gland occur after birth. Epigenetics is defined as the stable alterations in gene expression potential that arise during development and proliferation. Epigenetic changes are mediated at the biochemical level by the chromatin conformation initiated by DNA methylation, histone variants, and post-translational modifications of histones, non-histone chromatin proteins, and non-coding RNAs. Epigenetics plays a key role in development. However, very little is known about its role in the developing mammary gland, or how it might integrate the many signalling pathways involved in mammary gland development and function that have been discovered during the past few decades. An inverse relationship between marks of closed (DNA methylation), or open chromatin (DnaseI hypersensitivity, certain histone modifications) and milk protein gene expression has been documented. Recent studies have shown that during development and functional differentiation, both global and local chromatin changes occur. Locally, chromatin at distal regulatory elements and promoters of milk protein genes gains a more open conformation. Furthermore, changes occur both in looping between regulatory elements and attachment to nuclear matrix. These changes are induced by developmental signals and environmental conditions. Additionally, distinct epigenetic patterns have been identified in mammary gland stem and progenitor cell sub-populations. Together, these findings suggest that epigenetics plays a role in mammary development and function. With the new tools for epigenomics developed in recent years, we now can begin to establish a framework for the role of epigenetics in mammary gland development and disease.