Functional organization of the maternal and paternal human 4D Nucleome

人类父系和母系 4D 核组的功能组织

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作者:Stephen Lindsly, Wenlong Jia, Haiming Chen, Sijia Liu, Scott Ronquist, Can Chen, Xingzhao Wen, Cooper Stansbury, Gabrielle A Dotson, Charles Ryan, Alnawaz Rehemtulla, Gilbert S Omenn, Max Wicha, Shuai Cheng Li, Lindsey Muir, Indika Rajapakse

Abstract

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.

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