Peg1/Mest, an imprinted gene, is involved in mammary gland maturation

Abstract

Imprinted genes, which are specific to mammals, play important roles in cell proliferation, differentiation, ontogeny, and other phenomena. Moreover, these genes are considered crucial in the research of mammalian evolution. In the current study, we investigated the association between the expression of paternally imprinted gene paternally expressed 1/mesoderm-specific transcript (Peg1/Mest) and the maturation of the mammary gland. Quantitative real-time polymerase chain reaction analysis of Peg1/Mest gene expression at different stages of mouse mammary gland maturation revealed that its expression increased during gestation but decreased during lactation. Immunohistochemical staining demonstrated that Peg1/Mest was expressed in mammary epithelial cells. We measured expression levels of Peg1/Mest and E-cadherin during mammary alveoli formation using immunofluorescence staining a cell model for mammary alveoli formation in a 3D culture system. We found that the onset of E-cadherin expression roughly coincided with the peak of Peg1/Mest expression. Moreover, we discovered that the formation and proliferation of alveoli were suppressed in Peg1/Mest knockdown mammary epithelial cells. These results suggest that Peg1/Mest plays a certain role in mammary alveoli formation. To clarify the role of Peg1/Mest in the lactogenic differentiation of mammary epithelial cells, we examined the lactogenic differentiation capability of Peg1/Mest-overexpressing HC11 cells. Application of a differentiation-inducing stimulus did not increase β-casein expression in Peg1/Mest-overexpressing HC11 cells. The current study for the first time reports the involvement of an imprinted gene in mammary gland maturation.

The evolution of genomic imprinting: Epigenetic control of mammary gland development and postnatal resource control

“…Igf2, another imprinted gene expressed from the paternal allele, mediates prolactin-induced morphogenesis in the mammary gland (Brisken et al, 2002), and has been shown to be produced specifically by hormone-receptor positive cells in early pregnancy (De Silva, Kunasegaran, Ghosh, & Pietersen, 2015). Recently, it has been reported that paternally expressed Mest is involved in mammary gland maturation; specifically, its expression is increased during gestation contributing to the formation and proliferation of alveoli (Yonekura et al, 2019). The epithelium is not the only site for imprinted gene expression since a study found differential allelic expression of GNAS in human mammary adipose tissue samples (Klenke, Siffert, & Frey, 2011).…”

Marsupials have monoallelic MEST expression with a conserved antisense lncRNA but MEST is not imprinted

“…The short isoform of MEST was con rmed in both marsupials and platypus. Since this short isoform associates with mammary gland maturation in mice (Yonekura et al, 2019), it is possible that the evolution of the MEST isoform occurred with the evolution of the mammary gland in the common ancestor of mammals. However, the exact function of the MEST short isoform is currently unknown in any mammal.…”

“…Although its exact function is unknown, disruption of MEST imprinting causes developmental defects in placental and fetal growth and abnormal maternal behaviour in mice (Hiramuki et al, 2015;Lefebvre et al, 1998;Mayer et al, 2000). The MEST imprinted isoform also regulates mammary gland maturation in mice (Yonekura et al, 2019). Since the gene is associated with many classical mammal-speci c traits, characterising the evolution of this gene locus across mammals could shed light on how imprinting evolved in the common ancestor of therian mammals.…”

ZFP57 is a regulator of postnatal growth and life-long health

“…Previous studies have suggested that imprinting may be crucial in the mammary gland 2 , with some demonstrating functional roles for imprinted genes in this tissue 3,33 . However, although ZFP57 is a major regulator of imprinting, we show that it does not act through imprints in the mammary gland.…”