Orientation-dependent Dxz4 contacts shape the 3D structure of the inactive X chromosome
| Autor: | Joel B. Berletch, William Stafford Noble, Xinxian Deng, Ruolan Qui, Giancarlo Bonora, Vijay Ramani, Christine M. Disteche, Jay Schendure, Gala N Filippova, He Fang, Zhijun Duan |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
CCCTC-Binding Factor Amino Acid Motifs General Physics and Astronomy Plasma protein binding Epigenesis Genetic Mice 0302 clinical medicine X Chromosome Inactivation Gene expression lcsh:Science In Situ Hybridization Fluorescence X chromosome Genetics Physics Regulation of gene expression 0303 health sciences Multidisciplinary Dosage compensation Chromatin Cell biology Hinge region Protein Binding X Chromosome Science Locus (genetics) Biology Polymorphism Single Nucleotide Article General Biochemistry Genetics and Molecular Biology X-inactivation 03 medical and health sciences Animals Gene silencing Gene Silencing Epigenetics Alleles 030304 developmental biology Polymorphism Genetic General Chemistry DNA Methylation Mice Inbred C57BL 030104 developmental biology Gene Expression Regulation CTCF lcsh:Q Gene Deletion 030217 neurology & neurosurgery |
| Zdroj: | Nature Communications, Vol 9, Iss 1, Pp 1-17 (2018) Nature Communications |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-018-03694-y |
| Popis: | 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. The inactive X chromosome condenses into a bipartite structure. Here the authors use cells with allelic deletions or inversions to show that the Dxz4 locus is necessary to maintain the bipartite structure and that Dxz4 orientation controls the distribution of contacts on the inactive X chromosome. |
| Databáze: | OpenAIRE |
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