An Epigenetic Memory of Pregnancy in the Mouse Mammary Gland

Dos Santos, C. O., Dolzhenko, E., Hodges, E., Smith, A. D., Hannon, G. J. (May 2015) An Epigenetic Memory of Pregnancy in the Mouse Mammary Gland. Cell Reports. ISSN 2211-1247

URL: http://www.ncbi.nlm.nih.gov/pubmed/25959817
DOI: 10.1016/j.celrep.2015.04.015

Abstract

Pregnancy is the major modulator of mammary gland activity. It induces a tremendous expansion of the mammary epithelium and the generation of alveolar structures for milk production. Anecdotal evidence from multiparous humans indicates that the mammary gland may react less strongly to the first pregnancy than it does to subsequent pregnancies. Here, we verify that the mouse mammary gland responds more robustly to a second pregnancy, indicating that the gland retains a long-term memory of pregnancy. A comparison of genome-wide profiles of DNA methylation in isolated mammary cell types reveals substantial and long-lasting alterations. Since these alterations are maintained in the absence of the signal that induced them, we term them epigenetic. The majority of alterations in DNA methylation affect sites occupied by the Stat5a transcription factor and mark specific genes that are upregulated during pregnancy. We postulate that the epigenetic memory of a first pregnancy primes the activation of gene expression networks that promote mammary gland function in subsequent reproductive cycles. More broadly, our data indicate that physiological experience can broadly alter epigenetic states, functionally modifying the capacity of the affected cells to respond to later stimulatory events.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > epigenetics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > epigenetics

organs, tissues, organelles, cell types and functions > tissues types and functions > mammary gland
organism description > animal > mammal > rodent > mouse
CSHL Authors:
Communities: CSHL Cancer Center Program > Cancer Genetics
CSHL Cancer Center Program > Gene Regulation and Cell Proliferation
CSHL labs > Dos Santos lab
CSHL labs > Hannon lab
CSHL Cancer Center Shared Resources > Animal Services
Depositing User: Matt Covey
Date: 6 May 2015
Date Deposited: 19 May 2015 15:04
Last Modified: 05 Jan 2017 19:32
PMCID: PMC4439279
Related URLs:
URI: http://repository.cshl.edu/id/eprint/31514

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