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Epigenetic Modifications in 3D: Nuclear Organization of the Differentiating Mammary Epithelial Cell

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Abstract

During the development of tissues, complex programs take place to reach terminally differentiated states with specific gene expression profiles. Epigenetic regulations such as histone modifications and chromatin condensation have been implicated in the short and long-term control of transcription. It has recently been shown that the 3D spatial organization of chromosomes in the nucleus also plays a role in genome function. Indeed, the eukaryotic interphase nucleus contains sub-domains that are characterized by their enrichment in specific factors such as RNA Polymerase II, splicing machineries or heterochromatin proteins which render portions of the genome differentially permissive to gene expression. The positioning of individual genes relative to these sub-domains is thought to participate in the control of gene expression as an epigenetic mechanism acting in the nuclear space. Here, we review what is known about the sub-nuclear organization of mammary epithelial cells in connection with gene expression and epigenetics. Throughout differentiation, global changes in nuclear architecture occur, notably with respect to heterochromatin distribution. The positions of mammary-specific genes relative to nuclear sub-compartments varies in response to hormonal stimulation. The contribution of tissue architecture to cell differentiation in the mammary gland is also seen at the level of nuclear organization, which is sensitive to microenvironmental stimuli such as extracellular matrix signaling. In addition, alterations in nuclear organization are concomitant with immortalization and carcinogenesis. Thus, the fate of cells appears to be controlled by complex pathways connecting external signal integration, gene expression, epigenetic modifications and chromatin organization in the nucleus.

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Abbreviations

CSN:

casein

CT:

Chromosome Territory

ECM:

Extracellular Matrix

lrECM:

laminin-rich ECM

FISH:

Fluorescent In-Situ Hybridization

H3K9Me3:

Histone H3 Tri-methylated Lysine9

H4K20Me3:

Histone H4 Tri-methylated Lysine20

MEC:

Mammary Epithelial Cell

WAP:

whey acidic protein

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Acknowledgements

We would like to thank Christine Longin for performing electron microscopy studies and Violeta Chen for her assistance with the analysis of mouse mammary gland tissues.

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Authors and Affiliations

  1. UR1196 Génomique et Physiologie de la Lactation, INRA, Domaine de Vilvert, F-78352, Jouy-en-Josas, France

    Clémence Kress & Eve Devinoy

  2. Centre de Recerca en Sanitat Animal (CReSA), UAB-IRTA, Campus de la Universitat Autònoma de Barcelona, Bellaterra, Barcelona, 08193, Spain

    Maria Ballester

  3. USDA/ARS Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, 77030, USA

    Monique Rijnkels

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  1. Clémence Kress
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  2. Maria Ballester
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  3. Eve Devinoy
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  4. Monique Rijnkels
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Correspondence to Clémence Kress.

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Acknowledgement of financial support: Dr. M. Ballester has been financially supported by contract from the Juan de la Cierva program from the Spanish Ministry of Science and Innovation. INRA-292 and P00258 to Eve Devinoy, and USDA/ARS 6250-51000-048-00, and Department of Defense Breast Cancer Research Program W81XWH-05-01-0456 to Monique Rijnkels.

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Kress, C., Ballester, M., Devinoy, E. et al. Epigenetic Modifications in 3D: Nuclear Organization of the Differentiating Mammary Epithelial Cell. J Mammary Gland Biol Neoplasia 15, 73–83 (2010). https://doi.org/10.1007/s10911-010-9169-x

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