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PMID: 23301053 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Epigenetic modifications unlock the milk protein gene loci during mouse mammary gland development and differentiation.

PloS one ·Vol. 8 ·No. 1 ·2013-00-00 ·Pages e53270

Rijnkels M, Freeman-Zadrowski C, Hernandez J, Potluri V, Wang L, Li W, Lemay DG

Abstract

Unlike other tissues, development and differentiation of the mammary gland occur mostly after birth. The roles of systemic hormones and local growth factors important for this development and functional differentiation are well-studied. In other tissues, it has been shown that chromatin organization plays a key role in transcriptional regulation and underlies epigenetic regulation during development and differentiation. However, the role of chromatin organization in mammary gland development and differentiation is less well-defined. Here, we have studied the changes in chromatin organization at the milk protein gene loci (casein, whey acidic protein, and others) in the mouse mammary gland before and after functional differentiation. Distal regulatory elements within the casein gene cluster and whey acidic protein gene region have an open chromatin organization after pubertal development, while proximal promoters only gain open-chromatin marks during pregnancy in conjunction with the major induction of their expression. In contrast, other milk protein genes, such as alpha-lactalbumin, already have an open chromatin organization in the mature virgin gland. Changes in chromatin organization in the casein gene cluster region that are present after puberty persisted after lactation has ceased, while the changes which occurred during pregnancy at the gene promoters were not maintained. In general, mammary gland expressed genes and their regulatory elements exhibit developmental stage- and tissue-specific chromatin organization. A progressive gain of epigenetic marks indicative of open/active chromatin on genes marking functional differentiation accompanies the development of the mammary gland. These results support a model in which a chromatin organization is established during pubertal development that is then poised to respond to the systemic hormonal signals of pregnancy and lactation to achieve the full functional capacity of the mammary gland.

MeSH Terms
Albumins/metabolism Animals Cell Differentiation Chromatin/metabolism DNA Methylation Epigenesis, Genetic Female Gene Expression Regulation, Developmental Histones/metabolism Lactation Liver/metabolism Mammary Glands, Animal/embryology,growth & development Mice Milk Proteins/genetics,metabolism Promoter Regions, Genetic
Chemicals
Albumins Chromatin Histones Milk Proteins
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Rijnkels Monique
United States Department of Agriculture/Agriculture Research Service Children's Nutrition Research Center, Department of Pediatrics-Nutrition, Baylor College of Medicine, Houston, Texas, United States of America. rijnkel@bcm.edu
Freeman-Zadrowski Courtneay
Hernandez Joseph
Potluri Vani
Wang Liguo
Li Wei
Lemay Danielle G
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Article Info
Journal
PloS one
Abbr.
PLoS One
ISSN
1932-6203
DOI
10.1371/journal.pone.0053270
Email
rijnkel@bcm.edu
Published
2013-00-00
Epub
2013-00-02
Pages
e53270
Language
English
Region
United States
NLM ID
101285081
PMCID
PMC3534698
Subset
IM
Grants
NICHD NIH HHS · 1R03HD05609 · United States
NICHD NIH HHS · 1R21HD05376 · United States
Databases
GEO
GSE25105
External Links
PubMed source DOI: 10.1371/journal.pone.0053270 PMC Full Text View journal details
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