A self-enhanced transport mechanism through long noncoding RNAs for X chromosome inactivation.

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  • Additional Information
    • Source:
      Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
    • Publication Information:
      Original Publication: London : Nature Publishing Group, copyright 2011-
    • Subject Terms:
      X Chromosome Inactivation*; RNA, Long Noncoding/*metabolism; Animals ; Biological Transport ; Cell Lineage ; Embryonic Stem Cells/cytology ; Female ; Male ; Mice ; RNA, Long Noncoding/genetics ; Signal Transduction
    • Abstract:
      X-chromosome inactivation (XCI) is the mammalian dosage compensation strategy for balancing sex chromosome content between females and males. While works exist on initiation of symmetric breaking, the underlying allelic choice mechanisms and dynamic regulation responsible for the asymmetric fate determination of XCI remain elusive. Here we combine mathematical modeling and experimental data to examine the mechanism of XCI fate decision by analyzing the signaling regulatory circuit associated with long noncoding RNAs (lncRNAs) involved in XCI. We describe three plausible gene network models that incorporate features of lncRNAs in their localized actions and rapid transcriptional turnovers. In particular, we show experimentally that Jpx (a lncRNA) is transcribed biallelically, escapes XCI, and is asymmetrically dispersed between two X's. Subjecting Jpx to our test of model predictions against previous experimental observations, we identify that a self-enhanced transport feedback mechanism is critical to XCI fate decision. In addition, the analysis indicates that an ultrasensitive response of Jpx signal on CTCF is important in this mechanism. Overall, our combined modeling and experimental data suggest that the self-enhanced transport regulation based on allele-specific nature of lncRNAs and their temporal dynamics provides a robust and novel mechanism for bi-directional fate decisions in critical developmental processes.
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    • Grant Information:
      P50 GM076516 United States GM NIGMS NIH HHS; R01 GM107264 United States GM NIGMS NIH HHS; R01 NS095355 United States NS NINDS NIH HHS
    • Accession Number:
      0 (RNA, Long Noncoding)
    • Publication Date:
      Date Created: 20160817 Date Completed: 20180703 Latest Revision: 20240325
    • Publication Date:
      20240325
    • Accession Number:
      PMC4985753
    • Accession Number:
      10.1038/srep31517
    • Accession Number:
      27527711