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

   April 19th, 2018 at 3:33pm



The mammalian inactive X chromosome (Xi) condenses into a bipartite structure with two superdomains of frequent long-range contacts, separated by a hinge region. Using Hi-C in edited mouse cells with allelic deletions or inversions within the hinge, here we show that the conserved Dxz4 locus is necessary to maintain this bipartite structure. Dxz4 orientation controls the distribution of contacts on the Xi, as shown by a massive reversal in long-range contacts after Dxz4 inversion. Despite an increase in CTCF binding and chromatin accessibility on the Xi in Dxz4-edited cells, only minor changes in TAD structure and gene expression were detected, 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 its bank of CTCF motifs, which may work as a ratchet to form the distinctive bipartite structure of the condensed Xi.


Bonora G  •  Deng X  •  Fang H  •  Ramani V  •  Qiu R  •  Berletch JB  •  Filippova GN  •  Duan Z  •  Shendure J  •  Noble WS  •  Disteche CM



Nature communications



April 13th, 2018

About this study

This publication examines the functional elements within the hinge region which separates the inactive X chromosome into two super-domains. Allele-specific analyses including DNase Hi-C, ATAC-seq, CTCF ChIP-seq and RNA-seq were performed in wild-type and CRISPR-edited mouse F1 hybrid fibroblasts with the inactive X from BL6 (Patski; BL6/spretus). High-throughput sequencing datasets produced for this publication are shown in the interactive data matrix below and in the Experiment Sets tab.