Functional organization of the maternal and paternal human 4D Nucleome

Every human somatic cell inherits a maternal and a paternal genome, which work together to give rise to cellular phenotypes. However, the allele-specific relationship between gene expression and genome structure through the cell cycle is largely unknown. By integrating haplotype-resolved genome-wide chromosome conformation capture, mature and nascent mRNA, and protein binding data from a B lymphoblastoid cell line, we investigate this relationship both globally and locally. We introduce the maternal and paternal 4D Nucleome, enabling detailed analysis of the mechanisms and dynamics of genome structure and gene function for diploid organisms. Our analyses find significant coordination between allelic expression biases and local genome conformation, and notably absent expression bias in universally essential cell cycle and glycolysis genes. We propose a model in which coordinated biallelic expression reflects prioritized preservation of essential gene sets.

Automated summary

This study investigates the allele-specific relationship between gene expression and genome structure through the cell cycle using haplotype-resolved genome-wide chromosome conformation capture, mRNA, and protein binding data. The analysis reveals significant coordination between allelic expression biases and local genome conformation, with notably absent expression bias in certain essential genes, suggesting a prioritized preservation of essential gene sets. The study proposes a model in which coordinated biallelic expression reflects this prioritization.