title: Functional organization of the human 4D Nucleome.
abstract: The 4D organization of the interphase nucleus, or the 4D Nucleome (4DN), reflects a dynamical interaction between 3D genome structure and function and its relationship to phenotype. We present initial analyses of the human 4DN, capturing genome-wide structure using chromosome conformation capture and 3D imaging, and function using RNA-sequencing. We introduce a quantitative index that measures underlying topological stability of a genomic region. Our results show that structural features of genomic regions correlate with function with surprising persistence over time. Furthermore, constructing genome-wide gene-level contact maps aided in identifying gene pairs with high potential for coregulation and colocalization in a manner consistent with expression via transcription factories. We additionally use 2D phase planes to visualize patterns in 4DN data. Finally, we evaluated gene pairs within a circadian gene module using 3D imaging, and found periodicity in the movement of clock circadian regulator and period circadian clock 2 relative to each other that followed a circadian rhythm and entrained with their expression.
authors.affiliation: Department of Computational Medicine & Bioinformatics, Medical School, University of Michigan, Ann Arbor, MI 48109;
authors.forename: Haiming
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Computational Medicine & Bioinformatics, Medical School, University of Michigan, Ann Arbor, MI 48109; Department of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, MI 48109;
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Pediatrics-Pulmonary Medicine, Medical School, University of Michigan, Ann Arbor, MI 48109;
authors.forename: Lindsey A
authors.initials: LA
authors.lastname: Muir
authors.affiliation: Department of Computational Medicine & Bioinformatics, Medical School, University of Michigan, Ann Arbor, MI 48109;
authors.forename: Scott
authors.initials: S
authors.lastname: Ronquist
authors.affiliation: Department of Computational Medicine & Bioinformatics, Medical School, University of Michigan, Ann Arbor, MI 48109;
authors.forename: Walter
authors.initials: W
authors.lastname: Meixner
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109; Translational Oncology Program, Medical School, University of Michigan, Ann Arbor, MI 48109;
authors.forename: Mats
authors.initials: M
authors.lastname: Ljungman
authors.affiliation: Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;
authors.forename: Thomas
authors.initials: T
authors.lastname: Ried
authors.affiliation: Department of Mathematics, City University of Hong Kong, 999077 Hong Kong; Department of Mathematics, University of California, Berkeley, CA 94720;
authors.forename: Stephen
authors.initials: S
authors.lastname: Smale
authors.affiliation: Department of Computational Medicine & Bioinformatics, Medical School, University of Michigan, Ann Arbor, MI 48109; Translational Oncology Program, Medical School, University of Michigan, Ann Arbor, MI 48109; Department of Mathematics, College of Literature, Science, and the Arts, University of Michigan, Ann Arbor, MI 48109 indikar@umich.edu.
authors.forename: Indika
authors.initials: I
authors.lastname: Rajapakse
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism*; D002940:Circadian Rhythm / Q000235:genetics; D053263:Gene Regulatory Networks; D015894:Genome, Human; D006801:Humans; D007399:Interphase
keywords: 4D Nucleome; Laplacian; interphase nucleus; networks; phase plane