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The Epigenetic Landscape of Mammary Gland Development and Functional Differentiation

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Journal of Mammary Gland Biology and Neoplasia Aims and scope Submit manuscript

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.

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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

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Acknowledgement of financial support

USDA/ARS 6250-51000-048-00, NIH 1R21HD053762, and NIH 5R03HD56090 to MR; NIH R37-CA16303-35 to JMR; Iranian Ministry of Science, Research and Technology to MBMT and INRA-292 and P00258 to ED

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Authors and Affiliations

  1. USDA/ARS Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA

    Monique Rijnkels

  2. Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA

    Elena Kabotyanski & Jeffrey M. Rosen

  3. Department of Animal Science, Faculty of Agriculture, University of Birjand, Birjand, Iran

    Mohamad B. Montazer-Torbati

  4. INRA, UR1196 Génomique et Physiologie de la Lactation, 78352, Jouy-en-Josas, France

    C. Hue Beauvais & Eve Devinoy

  5. Université Paris-Sud 11 CNRS UMR 8126, Institut de Cancérologie Gustave-Roussy, 94805, Villejuif cedex, France

    Yegor Vassetzky

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  1. Monique Rijnkels
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  2. Elena Kabotyanski
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Correspondence to Monique Rijnkels.

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Rijnkels, M., Kabotyanski, E., Montazer-Torbati, M.B. et al. The Epigenetic Landscape of Mammary Gland Development and Functional Differentiation. J Mammary Gland Biol Neoplasia 15, 85–100 (2010). https://doi.org/10.1007/s10911-010-9170-4

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