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Review
. 2021 Jun 15:19:3589-3598.
doi: 10.1016/j.csbj.2021.06.018. eCollection 2021.

Understanding three-dimensional chromatin organization in diploid genomes

Jing Li  1 , Yu Lin  1 , Qianzi Tang  1 , Mingzhou Li  1
Affiliations
Review

Understanding three-dimensional chromatin organization in diploid genomes

Jing Li et al. Comput Struct Biotechnol J. .

Abstract

The three-dimensional (3D) organization of chromatin in the nucleus of diploid eukaryotic organisms has fascinated biologists for many years. Despite major progress in chromatin conformation studies, current knowledge regarding the spatial organization of diploid (maternal and paternal) genomes is still limited. Recent advances in Hi-C technology and data processing approaches have enabled construction of diploid Hi-C contact maps. These maps greatly accelerated the pace of novel discoveries in haplotype-resolved 3D genome studies, revealing the role of allele biased chromatin conformation in transcriptional regulation. Here, we review emerging concepts and haplotype phasing strategies of Hi-C data in 3D diploid genome studies. We discuss new insights on homologous chromosomal organization and the interplay between allelic biased chromatin architecture and several nuclear functions, explaining how haplotype-resolved Hi-C technologies have been used to resolve important biological questions.

Keywords: 3D nucleus; Allele specific gene regulation; Chromatin conformation; Hi-C; Homologous chromosomes; Inter-chromosomal interaction.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

None
Graphical abstract
Fig. 1
Fig. 1
Schematics of haplotype phasing strategies for Hi-C read pairs. (A) The strategy of haplotype phasing for paired-end Hi-C reads based on heterozygous variants. (B) Two local imputation phasing methods for Hi-C reads. Left: The haplotype imputation algorithm in Dip-C developed by Tan et al. . An unknown haplotype of chromatin contact (circled blue dot) can be imputed based on the statistical properties of interchromosomal and long-range intrachromosomal contacts (blue dots) in the super-elliptical neighborhood (light blue shaded area) of the unphased contact (circled blue dot). The plot is modified from Tan et al. . Right: A novel phasing technique for Hi-C data, named ‘HaploHiC’. A paired-end Hi-C read with no allele-specific SNV or short InDels (insertions and deletions) has its origin imputed using information from nearby reads. The ratios of paternally and maternally mapped reads in the flanking regions of the unknown-haplotype reads are used to determine the likelihood of a given parental origin of unknown-haplotype reads.
Fig. 2
Fig. 2
Schematics of highly structured homolog pairing in diploid genomes. (A) Haplotype-resolved Hi-C map of a diploid F1 hybrid, which is assumed to have three pairs of chromosomes. The three boxes on the map show the chromatin interactions within the haploid chromosome (cis contacts, box 1), between homologous chromosomes (trans homolog contacts, box 2), and between heterologous chromosomes (trans heterolog contacts, box 3). The t-homo diagonals along the main cis diagonal of the map indicate the homolog pairing. (B) Spatial organization of haploid-level chromosomes in the 3D nucleus of diploid F1 hybrids obtained by 3D modeling of the haploid-resolved Hi-C map. Cis (box 1), t-homo (box 2), and t-heter (box 3) contacts are indicated on the map. (C) Zoomed in Hi-C maps of boxes 1, 2, and 3 shown in (A). (D) Local contact map and 3D organization of variable homolog pairing. Homolog pairing encompasses tightly and loosely paired regions, and displays highly structured trans-domains and trans-interaction peaks.
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