title: Paternal RLIM/Rnf12 is a survival factor for milk-producing alveolar cells.
abstract: In female mouse embryos, somatic cells undergo a random form of X chromosome inactivation (XCI), whereas extraembryonic trophoblast cells in the placenta undergo imprinted XCI, silencing exclusively the paternal X chromosome. Initiation of imprinted XCI requires a functional maternal allele of the X-linked gene Rnf12, which encodes the ubiquitin ligase Rnf12/RLIM. We find that knockout (KO) of Rnf12 in female mammary glands inhibits alveolar differentiation and milk production upon pregnancy, with alveolar cells that lack RLIM undergoing apoptosis as they begin to differentiate. Genetic analyses demonstrate that these functions are mediated primarily by the paternal Rnf12 allele due to nonrandom maternal XCI in mammary epithelial cells. These results identify paternal Rnf12/RLIM as a critical survival factor for milk-producing alveolar cells and, together with population models, reveal implications of transgenerational epigenetic inheritance.
authors.affiliation: Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Baowei
authors.initials: B
authors.lastname: Jiao
authors.forename: Hong
authors.initials: H
authors.lastname: Ma
authors.forename: Maxim N
authors.initials: MN
authors.lastname: Shokhirev
authors.forename: Alexander
authors.initials: A
authors.lastname: Drung
authors.forename: Qin
authors.initials: Q
authors.lastname: Yang
authors.forename: JongDae
authors.initials: J
authors.lastname: Shin
authors.forename: Shaolei
authors.initials: S
authors.lastname: Lu
authors.forename: Meg
authors.initials: M
authors.lastname: Byron
authors.forename: Sundeep
authors.initials: S
authors.lastname: Kalantry
authors.forename: Arthur M
authors.initials: AM
authors.lastname: Mercurio
authors.forename: Jeanne B
authors.initials: JB
authors.lastname: Lawrence
authors.forename: Alexander
authors.initials: A
authors.lastname: Hoffmann
authors.forename: Ingolf
authors.initials: I
authors.lastname: Bach
mesh_terms: D000818:Animals; D002470:Cell Survival; D044127:Epigenesis, Genetic; D005260:Female; D018392:Genomic Imprinting; D008297:Male; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000502:physiology; D051379:Mice; D011247:Pregnancy; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D049951:X Chromosome Inactivation
chemical_list: C120758:Rlim protein, mouse; D044767:Ubiquitin-Protein Ligases