title: Integrating epigenomic data and 3D genomic structure with a new measure of chromatin assortativity.
abstract: Network analysis is a powerful way of modeling chromatin interactions. Assortativity is a network property used in social sciences to identify factors affecting how people establish social ties. We propose a new approach, using chromatin assortativity, to integrate the epigenomic landscape of a specific cell type with its chromatin interaction network and thus investigate which proteins or chromatin marks mediate genomic contacts.
  
  
  
  We use high-resolution promoter capture Hi-C and Hi-Cap data as well as ChIA-PET data from mouse embryonic stem cells to investigate promoter-centered chromatin interaction networks and calculate the presence of specific epigenomic features in the chromatin fragments constituting the nodes of the network. We estimate the association of these features with the topology of four chromatin interaction networks and identify features localized in connected areas of the network. Polycomb group proteins and associated histone marks are the features with the highest chromatin assortativity in promoter-centered networks. We then ask which features distinguish contacts amongst promoters from contacts between promoters and other genomic elements. We observe higher chromatin assortativity of the actively elongating form of RNA polymerase 2 (RNAPII) compared with inactive forms only in interactions between promoters and other elements.
  
  
  
  Contacts among promoters and between promoters and other elements have different characteristic epigenomic features. We identify a possible role for the elongating form of RNAPII in mediating interactions among promoters, enhancers, and transcribed gene bodies. Our approach facilitates the study of multiple genome-wide epigenomic profiles, considering network topology and allowing the comparison of chromatin interaction networks.
authors.affiliation: Structural Biology and BioComputing Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. vpancaldi@cnio.es.
authors.forename: Vera
authors.initials: V
authors.lastname: Pancaldi
authors.affiliation: Structural Biology and BioComputing Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Carrillo-de-Santa-Pau
authors.affiliation: Nuclear Dynamics Programme, The Babraham Institute, Cambridge, UK.
authors.forename: Biola Maria
authors.initials: BM
authors.lastname: Javierre
authors.affiliation: Structural Biology and BioComputing Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Juan
authors.affiliation: Nuclear Dynamics Programme, The Babraham Institute, Cambridge, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Fraser
authors.affiliation: Nuclear Dynamics Programme, The Babraham Institute, Cambridge, UK.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Spivakov
authors.affiliation: Structural Biology and BioComputing Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Valencia
authors.affiliation: Structural Biology and BioComputing Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. drico@cnio.es.
authors.forename: Daniel
authors.identifier: 0000-0002-6561-2310
authors.initials: D
authors.lastname: Rico
mesh_terms: D000818:Animals; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D019295:Computational Biology; D053595:Embryonic Stem Cells; D057890:Epigenomics; D016678:Genome; D042421:Histone Code / Q000235:genetics; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051379:Mice; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid
chemical_list: D002843:Chromatin; D006657:Histones
keywords: 3D genome; Assortativity; Chromatin Interaction Network; Embryonic stem cells; Enhancers; Epigenomics; Polycomb; Promoter Capture Hi-C; RNA polymerase