title: RLIM is dispensable for X-chromosome inactivation in the mouse embryonic epiblast.
abstract: 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.
authors.affiliation: Program in Gene Function and Expression, University of Massachusetts Medical School (UMMS), Worcester, Massachusetts 01605, USA.
authors.forename: JongDae
authors.initials: J
authors.lastname: Shin
authors.affiliation: Veterinary & Animal Sciences, University of Massachusetts Amherst, Amherst, Massachusetts 01003, USA.
authors.forename: Mary C
authors.initials: MC
authors.lastname: Wallingford
authors.affiliation: Department of Cell and Developmental Biology, UMMS, Worcester, Massachusetts 01605, USA.
authors.forename: Judith
authors.initials: J
authors.lastname: Gallant
authors.affiliation: Veterinary & Animal Sciences, University of Massachusetts Amherst, Amherst, Massachusetts 01003, USA.
authors.forename: Chelsea
authors.initials: C
authors.lastname: Marcho
authors.affiliation: 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.
authors.forename: Baowei
authors.initials: B
authors.lastname: Jiao
authors.affiliation: Department of Cell and Developmental Biology, UMMS, Worcester, Massachusetts 01605, USA.
authors.forename: Meg
authors.initials: M
authors.lastname: Byron
authors.affiliation: Ortenau Klinikum Lahr-Ettenheim, Institut für Pathologie, 77933 Lahr, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Bossenz
authors.affiliation: Department of Cell and Developmental Biology, UMMS, Worcester, Massachusetts 01605, USA.
authors.forename: Jeanne B
authors.initials: JB
authors.lastname: Lawrence
authors.affiliation: Department of Cell and Developmental Biology, UMMS, Worcester, Massachusetts 01605, USA.
authors.forename: Stephen N
authors.initials: SN
authors.lastname: Jones
authors.affiliation: Veterinary & Animal Sciences, University of Massachusetts Amherst, Amherst, Massachusetts 01003, USA.
authors.forename: Jesse
authors.initials: J
authors.lastname: Mager
authors.affiliation: 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.
authors.forename: Ingolf
authors.initials: I
authors.lastname: Bach
mesh_terms: D000818:Animals; D015536:Down-Regulation; D010064:Embryo Implantation; D004622:Embryo, Mammalian / Q000196:embryology / Q000378:metabolism; D005260:Female; D005855:Germ Layers / Q000196:embryology* / Q000378:metabolism*; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D017404:In Situ Hybridization, Fluorescence; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D051379:Mice; D018345:Mice, Knockout; D062085:RNA, Long Noncoding / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D049951:X Chromosome Inactivation / Q000235:genetics*
chemical_list: D006657:Histones; D062085:RNA, Long Noncoding; C077885:XIST non-coding RNA; C120758:Rlim protein, mouse; D044767:Ubiquitin-Protein Ligases; D008239:Lysine