Functional organization of the maternal and paternal human 4D Nucleome
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
Affiliations
Stephen Lindsly
Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA
Wenlong Jia
Department of Computer Science, City University of Hong Kong, Kowloon, Hong Kong
Haiming Chen
Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA
Sijia Liu
MIT-IBM Watson AI Lab, IBM Research, Cambridge, MA 02142, USA
Scott Ronquist
Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA
Can Chen
Department of Mathematics, University of Michigan, Ann Arbor, MI 48109, USA; Department of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, MI 48109, USA
Xingzhao Wen
Department of Bioengineering, University of California San Diego, La Jolla, CA 92093, USA
Cooper Stansbury
Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA
Gabrielle A. Dotson
Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA
Charles Ryan
Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA; Medical Scientist Training Program, University of Michigan, Ann Arbor, MI 48109, USA; Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, MI 48109, USA
Alnawaz Rehemtulla
Department of Hematology/Oncology, University of Michigan, Ann Arbor, MI 48109, USA
Gilbert S. Omenn
Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA; Department of Internal Medicine, Human Genetics, and School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA
Max Wicha
Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA; Department of Hematology/Oncology, University of Michigan, Ann Arbor, MI 48109, USA
Shuai Cheng Li
Department of Computer Science, City University of Hong Kong, Kowloon, Hong Kong
Lindsey Muir
Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA
Indika Rajapakse
Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA; Department of Mathematics, University of Michigan, Ann Arbor, MI 48109, USA; Corresponding author
Summary: 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.
