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Orientation-dependent Dxz4 contacts shape the 3D structure of the inactive X chromosome

View ORCID ProfileGiancarlo Bonora, Xinxian Deng, He Fang, Vijay Ramani, Ruolan Qui, Joel Berletch, Gala N Filippova, Zhijun Duan, Jay Schendure, William S Noble, Christine M Disteche
doi: https://doi.org/10.1101/165340
Giancarlo Bonora
University of Washington
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  • ORCID record for Giancarlo Bonora
Xinxian Deng
University of Washington
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He Fang
University of Washington
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Vijay Ramani
University of Washington
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Ruolan Qui
University of Washington
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Joel Berletch
University of Washington
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Gala N Filippova
University of Washington
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Zhijun Duan
University of Washington
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Jay Schendure
University of Washington
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William S Noble
University of Washington
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Christine M Disteche
University of Washington
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  • For correspondence: cdistech@u.washington.edu
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Abstract

The mammalian inactive X chromosome (Xi) condenses into a bipartite structure with two superdomains of frequent long-range contacts separated by a boundary or hinge region. Using in situ DNase Hi-C in mouse cells with deletions or inversions within the hinge we show that the conserved repeat locus Dxz4 alone is sufficient to maintain the bipartite structure and that Dxz4 orientation controls the distribution of long-range contacts on the Xi. Frequent long-range contacts between Dxz4 and the telomeric superdomain are either lost after its deletion or shifted to the centromeric superdomain after its inversion. This massive reversal in contact distribution is consistent with the reversal of CTCF motif orientation at Dxz4. De-condensation of the Xi after Dxz4 deletion is associated with partial restoration of TADs normally attenuated on the Xi, and with an increase in chromatin accessibility and CTCF binding on the Xi after Dxz4 deletion or inversion, but few changes in gene expression, in accordance with multiple epigenetic mechanisms ensuring X silencing. We propose that Dxz4 represents a structural platform for frequent long-range contacts with multiple loci in a direction dictated by the orientation of a bank of CTCF motifs at Dxz4, which may work as a ratchet to form the distinctive bipartite structure of the condensed Xi.

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  • Posted December 15, 2017.

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Orientation-dependent Dxz4 contacts shape the 3D structure of the inactive X chromosome
Giancarlo Bonora, Xinxian Deng, He Fang, Vijay Ramani, Ruolan Qui, Joel Berletch, Gala N Filippova, Zhijun Duan, Jay Schendure, William S Noble, Christine M Disteche
bioRxiv 165340; doi: https://doi.org/10.1101/165340
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Orientation-dependent Dxz4 contacts shape the 3D structure of the inactive X chromosome
Giancarlo Bonora, Xinxian Deng, He Fang, Vijay Ramani, Ruolan Qui, Joel Berletch, Gala N Filippova, Zhijun Duan, Jay Schendure, William S Noble, Christine M Disteche
bioRxiv 165340; doi: https://doi.org/10.1101/165340

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