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Although mammalian genomes are diploid, previous studies extensively investigated the average chromatin architectures without considering the differences between homologous chromosomes. We generated Hi-C, ChIP-seq, and RNA-seq data sets from CD4 T cells of B6, Cast, and hybrid mice, to investigate the diploid chromatin organization and epigenetic regulation. Our data indicate that inter-chromosomal interaction patterns between homologous chromosomes are similar, and the similarity is highly correlated with their allelic coexpression levels. Reconstruction of the 3D nucleus revealed that distances of the homologous chromosomes to the center of nucleus are almost the same. The inter-chromosomal interactions at centromere ends are significantly weaker than those at telomere ends, suggesting that they are located in different regions within the chromosome territories. The majority of A|B compartments or topologically associated domains (TADs) are consistent between B6 and Cast. We found 58% of the haploids in hybrids maintain their parental compartment status at B6/Cast divergent compartments owing to  cis  effect. About 95% of the  trans -effected B6/Cast divergent compartments converge to the same compartment status potentially because of a shared cellular environment. We showed the differentially expressed genes between the two haploids in hybrid were associated with either genetic or epigenetic effects. In summary, our multi-omics data from the hybrid mice provided haploid-specific information on the 3D nuclear architecture and a rich resource for further understanding the epigenetic regulation of haploid-specific gene expression.

Diploid genome architecture revealed by multi-omic data of hybrid mice