Bipartite structure of the inactive mouse X chromosome

• Published in: Genome Biology Vol. 16; no. 1; p. 152
• Main Authors: Deng, Xinxian, Ma, Wenxiu, Ramani, Vijay, Hill, Andrew, Yang, Fan, Ay, Ferhat, Berletch, Joel B., Blau, Carl Anthony, Shendure, Jay, Duan, Zhijun, Noble, William S., Disteche, Christine M.
• Format: Journal Article
• Language: English
• Published: England BioMed Central 07.08.2015
• Subjects: Alleles; Animals; Bioinformatics; CCCTC-Binding Factor; Cell Line; cell nucleolus; Cell Nucleolus - metabolism; Cells, Cultured; Chromatin; Chromosomes; Chromosomes, Human, X - chemistry; Deoxyribonuclease; deoxyribonucleases; DNA methylation; DNA-directed RNA polymerase; Epigenetics; Female; females; Gene expression; Gene silencing; Genomes; Genomic Imprinting; genomics; Humans; loci; Male; Mice; Nucleoli; Repressor Proteins - chemistry; Repressor Proteins - metabolism; RNA Polymerase II - chemistry; RNA Polymerase II - metabolism; Somatic cells; species; X Chromosome - chemistry; X Chromosome - metabolism; X Chromosome Inactivation; X Chromosomes
• ISSN: 1474-760X; 1474-7596; 1474-760X
• DOI: 10.1186/s13059-015-0728-8

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. 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. 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.