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.