Live-cell chromosome dynamics and outcome of X chromosome pairing events during ES cell differentiation.
Live-cell chromosome dynamics and outcome of X chromosome pairing events during ES cell differentiation.
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DOI：
10.1016/j.cell.2011.03.032
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发表时间：
2011-04-29
期刊：
影响因子：
64.5
通讯作者：
Heard E
中科院分区：
文献类型：
--
作者：
Masui O;Bonnet I;Le Baccon P;Brito I;Pollex T;Murphy N;Hupé P;Barillot E;Belmont AS;Heard E
随机X失活代表了早期胚胎干细胞分化过程中单等位基因调控的范例。在小鼠中，XX细胞中X染色体失活的选择是通过其反义转录单位Tsix/Xite对Xist RNA的单等位基因调控来保证的。同源配对事件被认为是不对称t6表达的基础，但由于其动态性和瞬态性，缺乏直接证据。在这里，我们研究了Tsix配对在小鼠胚胎干细胞分化中的活细胞动力学和结果。我们发现，在早期分化过程中，包括Xics在内的基因组动力学总体上有所增加。在配对过程中，Xic位点的运动明显减少。分离后，t6的表达变成短暂的单等位基因，为单等位基因的上调提供了机会。我们的研究结果揭示了X染色体在早期分化过程中的时空编排，并表明配对在X随机失活过程中促进对称破坏和单等位基因调控中的直接作用。
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.
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