University of Massachusetts Medical School Faculty Publications

UMMS Affiliation

Department of Molecular, Cell and Cancer Biology; Department of Biochemistry and Molecular Pharmacology; Department of Cell and Developmental Biology; Department of Neurology; UMass Metabolic Network; Lawrence Lab; Stephen Jones Lab; Department of Pediatrics

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Cell Biology | Cellular and Molecular Physiology | Developmental Biology


During female mouse embryogenesis, two forms of X chromosome inactivation (XCI) ensure dosage compensation from sex chromosomes. Beginning at the four-cell stage, imprinted XCI (iXCI) exclusively silences the paternal X (Xp), and this pattern is maintained in extraembryonic cell types. Epiblast cells, which give rise to the embryo proper, reactivate the Xp (XCR) and undergo a random form of XCI (rXCI) around implantation. Both iXCI and rXCI depend on the long non-coding RNA Xist. The ubiquitin ligase RLIM is required for iXCI in vivo and occupies a central role in current models of rXCI. Here, we demonstrate the existence of Rlim-dependent and Rlim-independent pathways for rXCI in differentiating female ESCs. Upon uncoupling these pathways, we find more efficient Rlim-independent XCI in ESCs cultured under physiological oxygen conditions. Our results revise current models of rXCI and suggest that caution must be taken when comparing XCI studies in ESCs and mice.


EB differentiation, ESC, Rlim, Rlim-independent XCI, Rnf12, X chromosome inactivation, XCI, XCI regulation, Xist, physiological oxygen levels

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Copyright 2017 The Author(s). This is an open access article under the CC BY-NC-ND license (

DOI of Published Version



Cell Rep. 2017 Dec 26;21(13):3691-3699. doi: 10.1016/j.celrep.2017.12.004. Link to article on publisher's site

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Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.



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