1. Developmental Biology
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Regulation of X-linked gene expression during early mouse development by Rlim

  1. Feng Wang
  2. JongDae Shin
  3. Jeremy M Shea
  4. Jun Yu
  5. Ana Bošković
  6. Meg Byron
  7. Xiaochun Zhu
  8. Alex K Shalek
  9. Aviv Regev
  10. Jeanne B Lawrence
  11. Eduardo M Torres
  12. Lihua J Zhu
  13. Oliver J Rando
  14. Ingolf Bach  Is a corresponding author
  1. University of Massachusetts Medical School, United States
  2. Massachusetts Institute of Technology, United States
  3. Broad Institute of MIT and Harvard, United States
Research Article
  • Cited 16
  • Views 1,712
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Cite this article as: eLife 2016;5:e19127 doi: 10.7554/eLife.19127

Abstract

Mammalian X-linked gene expression is highly regulated as female cells contain two and male one X chromosome (X). To adjust the X gene dosage between genders, female mouse preimplantation embryos undergo an imprinted form of X chromosome inactivation (iXCI) that requires both Rlim (also known as Rnf12) and the long non-coding RNA Xist. Moreover, it is thought that gene expression from the single active X is upregulated to correct for bi-allelic autosomal (A) gene expression. We have combined mouse genetics with RNA-seq on single mouse embryos to investigate functions of Rlim on the temporal regulation of iXCI and Xist. Our results reveal crucial roles of Rlim for the maintenance of high Xist RNA levels, Xist clouds and X-silencing in female embryos at blastocyst stages, while initial Xist expression appears Rlim-independent. We find further that X/A upregulation is initiated in early male and female preimplantation embryos.

Article and author information

Author details

  1. Feng Wang

    Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    No competing interests declared.
  2. JongDae Shin

    Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    No competing interests declared.
  3. Jeremy M Shea

    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    No competing interests declared.
  4. Jun Yu

    Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    No competing interests declared.
  5. Ana Bošković

    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    No competing interests declared.
  6. Meg Byron

    Department of Cell and Developmental Biology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    No competing interests declared.
  7. Xiaochun Zhu

    Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    No competing interests declared.
  8. Alex K Shalek

    Department of Chemistry and Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, United States
    Competing interests
    No competing interests declared.
  9. Aviv Regev

    Broad Institute of MIT and Harvard, Cambridge, United States
    Competing interests
    Aviv Regev, Senior editor, eLife.
  10. Jeanne B Lawrence

    Department of Cell and Developmental Biology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    No competing interests declared.
  11. Eduardo M Torres

    Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    No competing interests declared.
  12. Lihua J Zhu

    Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    No competing interests declared.
  13. Oliver J Rando

    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    No competing interests declared.
  14. Ingolf Bach

    Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, United States
    For correspondence
    ingolf.bach@umassmed.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4505-8946

Funding

National Institutes of Health (R01CA131158)

  • Ingolf Bach

National Institutes of Health (R01HD080224)

  • Oliver J Rando

National Institutes of Health (DP1ES025458)

  • Oliver J Rando

National Institutes of Health (R01GM053234)

  • Jeanne B Lawrence

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All mice were housed in the animal facility of UMMS, and utilized according to NIH guidelines and those established by the UMMS Institute of Animal Care and Usage Committee (IACUC protocol #: A-1940-14).

Reviewing Editor

  1. Kevin Struhl, Harvard Medical School, United States

Publication history

  1. Received: June 26, 2016
  2. Accepted: September 15, 2016
  3. Accepted Manuscript published: September 19, 2016 (version 1)
  4. Accepted Manuscript updated: September 20, 2016 (version 2)
  5. Accepted Manuscript updated: September 20, 2016 (version 3)
  6. Accepted Manuscript updated: September 20, 2016 (version 4)
  7. Version of Record published: October 11, 2016 (version 5)

Copyright

© 2016, Wang et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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