title: Mining 3D genome structure populations identifies major factors governing the stability of regulatory communities.
abstract: Three-dimensional (3D) genome structures vary from cell to cell even in an isogenic sample. Unlike protein structures, genome structures are highly plastic, posing a significant challenge for structure-function mapping. Here we report an approach to comprehensively identify 3D chromatin clusters that each occurs frequently across a population of genome structures, either deconvoluted from ensemble-averaged Hi-C data or from a collection of single-cell Hi-C data. Applying our method to a population of genome structures (at the macrodomain resolution) of lymphoblastoid cells, we identify an atlas of stable inter-chromosomal chromatin clusters. A large number of these clusters are enriched in binding of specific regulatory factors and are therefore defined as 'Regulatory Communities.' We reveal two major factors, centromere clustering and transcription factor binding, which significantly stabilize such communities. Finally, we show that the regulatory communities differ substantially from cell to cell, indicating that expression variability could be impacted by genome structures.
authors.affiliation: Molecular and Computational Biology, Department of Biological Sciences, University of Southern California, 1050 Childs Way, Los Angeles, California 90089, USA.
authors.forename: Chao
authors.initials: C
authors.lastname: Dai
authors.affiliation: Molecular and Computational Biology, Department of Biological Sciences, University of Southern California, 1050 Childs Way, Los Angeles, California 90089, USA.
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Li
authors.affiliation: Molecular and Computational Biology, Department of Biological Sciences, University of Southern California, 1050 Childs Way, Los Angeles, California 90089, USA.
authors.forename: Harianto
authors.initials: H
authors.lastname: Tjong
authors.affiliation: Molecular and Computational Biology, Department of Biological Sciences, University of Southern California, 1050 Childs Way, Los Angeles, California 90089, USA.
authors.forename: Shengli
authors.initials: S
authors.lastname: Hao
authors.affiliation: Molecular and Computational Biology, Department of Biological Sciences, University of Southern California, 1050 Childs Way, Los Angeles, California 90089, USA.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Molecular and Computational Biology, Department of Biological Sciences, University of Southern California, 1050 Childs Way, Los Angeles, California 90089, USA.
authors.forename: Qingjiao
authors.initials: Q
authors.lastname: Li
authors.affiliation: Molecular and Computational Biology, Department of Biological Sciences, University of Southern California, 1050 Childs Way, Los Angeles, California 90089, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Zhu
authors.affiliation: Molecular and Computational Biology, Department of Biological Sciences, University of Southern California, 1050 Childs Way, Los Angeles, California 90089, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Alber
authors.affiliation: Molecular and Computational Biology, Department of Biological Sciences, University of Southern California, 1050 Childs Way, Los Angeles, California 90089, USA.
authors.forename: Xianghong
authors.initials: X
authors.lastname: Jasmine Zhou
mesh_terms: D002460:Cell Line; D002503:Centromere / Q000235:genetics / Q000378:metabolism; D002843:Chromatin / Q000737:chemistry / Q000235:genetics*; D002877:Chromosomes, Human / Q000737:chemistry / Q000235:genetics*; D019295:Computational Biology / Q000379:methods*; D057225:Data Mining / Q000379:methods*; D015894:Genome, Human / Q000235:genetics; D042822:Genomic Instability / Q000235:genetics; D023281:Genomics / Q000379:methods*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D011485:Protein Binding / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D002843:Chromatin; D014157:Transcription Factors