Live-cell chromosome dynamics and outcome of X chromosome pairing events during ES cell differentiation

Osamu Masui, Isabelle Bonnet, Patricia Le Baccon, Isabel Brito, Tim Pollex, Niall Murphy, Philippe Hupé, Emmanuel Barillot, Andrew S. Belmont, Edith Heard

Research output: Contribution to journalArticle

Abstract

Random X inactivation represents a paradigm for monoallelic gene regulation during early ES cell differentiation. In mice, the choice of X chromosome to inactivate in XX cells is ensured by monoallelic regulation of Xist RNA via its antisense transcription unit Tsix/Xite. Homologous pairing events have been proposed to underlie asymmetric Tsix expression, but direct evidence has been lacking owing to their dynamic and transient nature. Here we investigate the live-cell dynamics and outcome of Tsix pairing in differentiating mouse ES cells. We find an overall increase in genome dynamics including the Xics during early differentiation. During pairing, however, Xic loci show markedly reduced movements. Upon separation, Tsix expression becomes transiently monoallelic, providing a window of opportunity for monoallelic Xist upregulation. Our findings reveal the spatiotemporal choreography of the X chromosomes during early differentiation and indicate a direct role for pairing in facilitating symmetry-breaking and monoallelic regulation of Xist during random X inactivation.

Original languageEnglish (US)
Pages (from-to)447-458
Number of pages12
JournalCell
Volume145
Issue number3
DOIs
StatePublished - Apr 29 2011

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Masui, O., Bonnet, I., Le Baccon, P., Brito, I., Pollex, T., Murphy, N., Hupé, P., Barillot, E., Belmont, A. S., & Heard, E. (2011). Live-cell chromosome dynamics and outcome of X chromosome pairing events during ES cell differentiation. Cell, 145(3), 447-458. https://doi.org/10.1016/j.cell.2011.03.032