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A prominent and conserved role for YY1 in Xist transcriptional activation

Author

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  • Mélanie Makhlouf

    (CNRS, UMR7216 Epigenetics and Cell Fate
    Univ Paris Diderot, Sorbonne Paris Cité)

  • Jean-François Ouimette

    (CNRS, UMR7216 Epigenetics and Cell Fate
    Univ Paris Diderot, Sorbonne Paris Cité)

  • Andrew Oldfield

    (CNRS, UMR7216 Epigenetics and Cell Fate
    Univ Paris Diderot, Sorbonne Paris Cité
    Present address: NIEHS, Laboratory of Molecular Carcinogenesis, Systems Biology, Research Triangle Park, North Carolina 27709, USA)

  • Pablo Navarro

    (CNRS, URA2578 Institute Pasteur)

  • Damien Neuillet

    (CNRS, UMR7216 Epigenetics and Cell Fate
    Univ Paris Diderot, Sorbonne Paris Cité)

  • Claire Rougeulle

    (CNRS, UMR7216 Epigenetics and Cell Fate
    Univ Paris Diderot, Sorbonne Paris Cité)

Abstract

Accumulation of the noncoding RNA Xist on one X chromosome in female cells is a hallmark of X-chromosome inactivation (XCI) in eutherians. Here we uncover an essential function for the ubiquitous autosomal transcription factor Yin-Yang 1 (YY1) in the transcriptional activation of Xist in both human and mouse. We show that loss of YY1 prevents Xist upregulation during the initiation and maintenance of X-inactivation, and that YY1 binds directly the Xist 5′ region to trigger the activity of the Xist promoter. Binding of YY1 to the Xist 5′ region before XCI competes with the Xist repressor REX1, whereas DNA methylation controls mono-allelic fixation of YY1 to Xist at the onset of XCI. YY1 is thus the first autosomal activating factor involved in a fundamental and conserved pathway of Xist regulation that ensures the asymmetric transcriptional upregulation of the master regulator of XCI.

Suggested Citation

  • Mélanie Makhlouf & Jean-François Ouimette & Andrew Oldfield & Pablo Navarro & Damien Neuillet & Claire Rougeulle, 2014. "A prominent and conserved role for YY1 in Xist transcriptional activation," Nature Communications, Nature, vol. 5(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5878
    DOI: 10.1038/ncomms5878
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    Cited by:

    1. Andrew Keniry & Natasha Jansz & Linden J. Gearing & Iromi Wanigasuriya & Joseph Chen & Christian M. Nefzger & Peter F. Hickey & Quentin Gouil & Joy Liu & Kelsey A. Breslin & Megan Iminitoff & Tamara B, 2022. "BAF complex-mediated chromatin relaxation is required for establishment of X chromosome inactivation," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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