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
Publication Date
2017-12-26
Document Type
Article
Disciplines
Cell Biology | Cellular and Molecular Physiology | Developmental Biology
Abstract
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.
Keywords
EB differentiation, ESC, Rlim, Rlim-independent XCI, Rnf12, X chromosome inactivation, XCI, XCI regulation, Xist, physiological oxygen levels
Rights and Permissions
Copyright 2017 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
DOI of Published Version
10.1016/j.celrep.2017.12.004
Source
Cell Rep. 2017 Dec 26;21(13):3691-3699. doi: 10.1016/j.celrep.2017.12.004. Link to article on publisher's site
Related Resources
Journal/Book/Conference Title
Cell reports
PubMed ID
29281819
Repository Citation
Wang F, McCannell KN, Boskovic A, Zhu X, Shin J, Yu J, Gallant J, Byron M, Lawrence JB, Zhu LJ, Jones SN, Rando OJ, Fazzio TG, Bach I. (2017). Rlim-Dependent and -Independent Pathways for X Chromosome Inactivation in Female ESCs. University of Massachusetts Medical School Faculty Publications. https://doi.org/10.1016/j.celrep.2017.12.004. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/1473
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Included in
Cell Biology Commons, Cellular and Molecular Physiology Commons, Developmental Biology Commons