Bipartite structure of the inactive mouse X chromosome

Xinxian Deng, Wenxiu Ma, Vijay Ramani, Andrew Hill, Fan Yang, Ferhat Ay, Joel B. Berletch, Carl Anthony Blau, Jay Shendure, Zhijun Duan*, William S. Noble, Christine M. Disteche

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    114 Scopus citations

    Abstract

    Background: In mammals, one of the female X chromosomes and all imprinted genes are expressed exclusively from a single allele in somatic cells. To evaluate structural changes associated with allelic silencing, we have applied a recently developed Hi-C assay that uses DNase I for chromatin fragmentation to mouse F1 hybrid systems. Results: We find radically different conformations for the two female mouse X chromosomes. The inactive X has two superdomains of frequent intrachromosomal contacts separated by a boundary region. Comparison with the recently reported two-superdomain structure of the human inactive X shows that the genomic content of the superdomains differs between species, but part of the boundary region is conserved and located near the Dxz4/DXZ4 locus. In mouse, the boundary region also contains a minisatellite, Ds-TR, and both Dxz4 and Ds-TR appear to be anchored to the nucleolus. Genes that escape X inactivation do not cluster but are located near the periphery of the 3D structure, as are regions enriched in CTCF or RNA polymerase. Fewer short-range intrachromosomal contacts are detected for the inactive alleles of genes subject to X inactivation compared with the active alleles and with genes that escape X inactivation. This pattern is also evident for imprinted genes, in which more chromatin contacts are detected for the expressed allele. Conclusions: By applying a novel Hi-C method to map allelic chromatin contacts, we discover a specific bipartite organization of the mouse inactive X chromosome that probably plays an important role in maintenance of gene silencing.

    Original languageEnglish (US)
    Article number152
    JournalGenome biology
    Volume16
    Issue number1
    DOIs
    StatePublished - Aug 7 2015

    ASJC Scopus subject areas

    • Ecology, Evolution, Behavior and Systematics
    • Genetics
    • Cell Biology

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