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

  1. Wenfei Jin1
  1. 1Department of Biology, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China;
  2. 2Institute of Life Sciences, Southeast University, Nanjing, Jiangsu 210096, China;
  3. 3Systems Biology Center, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
  • Corresponding authors: jinwf{at}sustech.edu.cn, zhaok{at}nhlbi.nih.gov
  • Abstract

    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.

    Footnotes

    • Received September 26, 2019.
    • Accepted July 23, 2020.

    This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.

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