Publication Date:
2014-05-30
Description:
In female mice, two forms of X-chromosome inactivation (XCI) ensure the selective silencing of female sex chromosomes during mouse embryogenesis. Beginning at the four-cell stage, imprinted XCI (iXCI) exclusively silences the paternal X chromosome. Later, around implantation, epiblast cells of the inner cell mass that give rise to the embryo reactivate the paternal X chromosome and undergo a random form of XCI (rXCI). Xist, a long non-coding RNA crucial for both forms of XCI, is activated by the ubiquitin ligase RLIM (also known as Rnf12). Although RLIM is required for triggering iXCI in mice, its importance for rXCI has been controversial. Here we show that RLIM levels are downregulated in embryonic cells undergoing rXCI. Using mouse genetics we demonstrate that female cells lacking RLIM from pre-implantation stages onwards show hallmarks of XCI, including Xist clouds and H3K27me3 foci, and have full embryogenic potential. These results provide evidence that RLIM is dispensable for rXCI, indicating that in mice an RLIM-independent mechanism activates Xist in the embryo proper.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4105192/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4105192/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shin, JongDae -- Wallingford, Mary C -- Gallant, Judith -- Marcho, Chelsea -- Jiao, Baowei -- Byron, Meg -- Bossenz, Michael -- Lawrence, Jeanne B -- Jones, Stephen N -- Mager, Jesse -- Bach, Ingolf -- CA077735/CA/NCI NIH HHS/ -- CA131158/CA/NCI NIH HHS/ -- DK32520/DK/NIDDK NIH HHS/ -- GM053234/GM/NIGMS NIH HHS/ -- R01 CA131158/CA/NCI NIH HHS/ -- R01 GM053234/GM/NIGMS NIH HHS/ -- England -- Nature. 2014 Jul 3;511(7507):86-9. doi: 10.1038/nature13286. Epub 2014 May 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program in Gene Function and Expression, University of Massachusetts Medical School (UMMS), Worcester, Massachusetts 01605, USA. ; Veterinary & Animal Sciences, University of Massachusetts Amherst, Amherst, Massachusetts 01003, USA. ; Department of Cell and Developmental Biology, UMMS, Worcester, Massachusetts 01605, USA. ; 1] Program in Gene Function and Expression, University of Massachusetts Medical School (UMMS), Worcester, Massachusetts 01605, USA [2] Kunming Institute of Zoology, Chinese Academy of Science, Kunming 650223, China. ; Ortenau Klinikum Lahr-Ettenheim, Institut fur Pathologie, 77933 Lahr, Germany. ; 1] Program in Gene Function and Expression, University of Massachusetts Medical School (UMMS), Worcester, Massachusetts 01605, USA [2] Program in Molecular Medicine, UMMS, Worcester, Massachusetts 01605, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24870238" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Down-Regulation
;
Embryo Implantation
;
Embryo, Mammalian/embryology/metabolism
;
Female
;
Germ Layers/*embryology/*metabolism
;
Histones/chemistry/metabolism
;
In Situ Hybridization, Fluorescence
;
Lysine/metabolism
;
Methylation
;
Mice
;
Mice, Knockout
;
RNA, Long Noncoding/genetics
;
Ubiquitin-Protein Ligases/genetics/*metabolism
;
X Chromosome Inactivation/*genetics
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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