摘要:SummaryEvery 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.Graphical abstractDisplay OmittedHighlights•We discover allele-specific relationships in genome architecture and gene expression•Integration of data modalities reveals an allele-specific 4D Nucleome•Allelic expression and conformation biases correspond to Pol II recruitment biases•We introduce a novel haplotype phasing algorithm, HaploHiCGenomics; Bioinformatics; Genomic analysis