Document Detail


Paternal RLIM/Rnf12 is a survival factor for milk-producing alveolar cells.
MedLine Citation:
PMID:  22541433     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Baowei Jiao; Hong Ma; Maxim N Shokhirev; Alexander Drung; Qin Yang; JongDae Shin; Shaolei Lu; Meg Byron; Sundeep Kalantry; Arthur M Mercurio; Jeanne B Lawrence; Alexander Hoffmann; Ingolf Bach
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Cell     Volume:  149     ISSN:  1097-4172     ISO Abbreviation:  Cell     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-04-30     Completed Date:  2012-06-22     Revised Date:  2013-06-25    
Medline Journal Info:
Nlm Unique ID:  0413066     Medline TA:  Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  630-41     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
Affiliation:
Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, MA 01605, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Survival*
Epigenesis, Genetic
Female
Genomic Imprinting
Male
Mammary Glands, Animal / cytology*,  physiology
Mice
Pregnancy
Ubiquitin-Protein Ligases / genetics,  metabolism*
X Chromosome Inactivation
Grant Support
ID/Acronym/Agency:
R01 CA131158/CA/NCI NIH HHS; R01 CA131158-04/CA/NCI NIH HHS; R01CA131158/CA/NCI NIH HHS; R01CA89209/CA/NCI NIH HHS; R01GM053234/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
EC 6.3.2.-/Rlim protein, mouse; EC 6.3.2.19/Ubiquitin-Protein Ligases
Comments/Corrections

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