Journal of Mammary Gland Biology and Neoplasia

, Volume 15, Issue 1, pp 85–100

The Epigenetic Landscape of Mammary Gland Development and Functional Differentiation

  • Monique Rijnkels
  • Elena Kabotyanski
  • Mohamad B. Montazer-Torbati
  • C. Hue Beauvais
  • Yegor Vassetzky
  • Jeffrey M. Rosen
  • Eve Devinoy
Article

DOI: 10.1007/s10911-010-9170-4

Cite this article as:
Rijnkels, M., Kabotyanski, E., Montazer-Torbati, M.B. et al. J Mammary Gland Biol Neoplasia (2010) 15: 85. doi:10.1007/s10911-010-9170-4

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, 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.

Keywords

Mammary glandEpigeneticMilk protein genesChromatinDevelopment

Abbreviations

BCE

beta casein enhancer

C/EBPβ

CCAAT-enhancer-binding proteins

ChIP

chromatin immunoprecipitation

DNAme

DNA methylation

DHS

DNaseI hypersensitivity

DRE

distal regulatory elements

ECR

evolutionary conserved regions

EMSA

Electro Mobility Shift Assay

Gc

glucocorticoid

GR

glucocorticoid receptor

MEC

mammary epithelial cell

Pg

progesterone

PR

progesterone receptor

Prl

prolactin

ncRNA

non-coding RNA

STAT5

signal transducers and activators of transcription

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Monique Rijnkels
    • 1
  • Elena Kabotyanski
    • 2
  • Mohamad B. Montazer-Torbati
    • 3
  • C. Hue Beauvais
    • 4
  • Yegor Vassetzky
    • 5
  • Jeffrey M. Rosen
    • 2
  • Eve Devinoy
    • 4
  1. 1.USDA/ARS Children’s Nutrition Research Center, Department of PediatricsBaylor College of MedicineHoustonUSA
  2. 2.Department of Molecular and Cellular BiologyBaylor College of MedicineHoustonUSA
  3. 3.Department of Animal Science, Faculty of AgricultureUniversity of BirjandBirjandIran
  4. 4.INRA, UR1196 Génomique et Physiologie de la LactationJouy-en-JosasFrance
  5. 5.Université Paris-Sud 11 CNRS UMR 8126, Institut de Cancérologie Gustave-RoussyVillejuif cedexFrance