Abstract
BackgroundUnlike 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.Methodology/Principal FindingsDistal 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.Conclusions/SignificanceA 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.
Highlights
Mammary glands are unique to mammals and are the basis of the survival and existence of these species
Using comparative genome analysis we have previously identified evolutionary conserved regions (ECRs) in the casein gene cluster [35,36] and a number of distal regulatory elements have been identified for the mouse whey acidic protein gene (Wap) [17,37,38,39]
Open chromatin structure is expected on regulatory elements of genes expressed during lactation in the lactating mammary gland, while a closed chromatin structure is expected on regulatory elements of non-expressed genes
Summary
Mammary glands are unique to mammals and are the basis of the survival and existence of these species. Unlike most organs and tissues, which undergo most of their development in utero, the mammary gland develops primarily after birth. Once lactation ceases the gland undergoes remodeling, during which the majority of alveolar epithelial cells that previously secreted milk are lost. These postnatal developmental changes make the mammary gland an ideal model to study the regulation of developmental processes. Development and differentiation of the mammary gland occur mostly after birth. The role of chromatin organization in mammary gland development and differentiation is less well-defined. 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
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
