title: Topoisomerase II beta interacts with cohesin and CTCF at topological domain borders.
abstract: Type II DNA topoisomerases (TOP2) regulate DNA topology by generating transient double stranded breaks during replication and transcription. Topoisomerase II beta (TOP2B) facilitates rapid gene expression and functions at the later stages of development and differentiation. To gain new insight into the genome biology of TOP2B, we used proteomics (BioID), chromatin immunoprecipitation, and high-throughput chromosome conformation capture (Hi-C) to identify novel proximal TOP2B protein interactions and characterize the genomic landscape of TOP2B binding at base pair resolution.
  
  
  
  Our human TOP2B proximal protein interaction network included members of the cohesin complex and nucleolar proteins associated with rDNA biology. TOP2B associates with DNase I hypersensitivity sites, allele-specific transcription factor (TF) binding, and evolutionarily conserved TF binding sites on the mouse genome. Approximately half of all CTCF/cohesion-bound regions coincided with TOP2B binding. Base pair resolution ChIP-exo mapping of TOP2B, CTCF, and cohesin sites revealed a striking structural ordering of these proteins along the genome relative to the CTCF motif. These ordered TOP2B-CTCF-cohesin sites flank the boundaries of topologically associating domains (TADs) with TOP2B positioned externally and cohesin internally to the domain loop.
  
  
  
  TOP2B is positioned to solve topological problems at diverse cis-regulatory elements and its occupancy is a highly ordered and prevalent feature of CTCF/cohesin binding sites that flank TADs.
authors: Genetics and Genome Biology Program, SickKids Research Institute, Toronto, ON, Canada.|Department of Gene Technology, Tallinn University of Technology, Tallinn, Estonia.
authors: Liis
authors: L
authors: Uusküla-Reimand
authors: Genetics and Genome Biology Program, SickKids Research Institute, Toronto, ON, Canada.|Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
authors: Huayun
authors: H
authors: Hou
authors: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
authors: Payman
authors: P
authors: Samavarchi-Tehrani
authors: Research Department of Cancer Biology, Cancer Institute, University College London, London, UK.
authors: Matteo Vietri
authors: MV
authors: Rudan
authors: Genetics and Genome Biology Program, SickKids Research Institute, Toronto, ON, Canada.|Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
authors: Minggao
authors: M
authors: Liang
authors: Genetics and Genome Biology Program, SickKids Research Institute, Toronto, ON, Canada.|Present address: International Laboratory for Research in Human Genomics, Universidad Nacional Autónoma de México, Juriquilla, Querétaro, Mexico.
authors: Alejandra
authors: A
authors: Medina-Rivera
authors: Cancer Research UK, Cambridge Institute, University of Cambridge, Cambridge, UK.|Present address: The Babraham Institute, Cambridge, UK.
authors: Hisham
authors: H
authors: Mohammed
authors: Cancer Research UK, Cambridge Institute, University of Cambridge, Cambridge, UK.|Present address: Syncona Partners LLP, London, UK.
authors: Dominic
authors: D
authors: Schmidt
authors: European Molecular Biology Laboratory, European Bioinformatics Institute, Cambridge, UK.|Present address: Laboratory of Systems Biology and Genetics, Lausanne, Switzerland.
authors: Petra
authors: P
authors: Schwalie
authors: Genetics and Genome Biology Program, SickKids Research Institute, Toronto, ON, Canada.
authors: Edwin J
authors: EJ
authors: Young
authors: Ontario Institute for Cancer Research, Toronto, ON, Canada.|Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
authors: Jüri
authors: J
authors: Reimand
authors: Research Department of Cancer Biology, Cancer Institute, University College London, London, UK.
authors: Suzana
authors: S
authors: Hadjur
authors: Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.|Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
authors: Anne-Claude
authors: AC
authors: Gingras
authors: Genetics and Genome Biology Program, SickKids Research Institute, Toronto, ON, Canada. michael.wilson@sickkids.ca.|Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada. michael.wilson@sickkids.ca.
authors: Michael D
authors: MD
authors: Wilson
mesh_terms: D000483:Alleles; D000818:Animals; D001665:Binding Sites; D000076246:CCCTC-Binding Factor; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D002843:Chromatin / Q000235:genetics; D047369:Chromatin Immunoprecipitation; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism; D002875:Chromosomes; D004250:DNA Topoisomerases, Type II / Q000235:genetics* / Q000378:metabolism; D004275:DNA, Ribosomal / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D016678:Genome; D006801:Humans; D051379:Mice; D000075223:Poly-ADP-Ribose Binding Proteins; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D060066:Protein Interaction Maps / Q000235:genetics*; D040901:Proteomics; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D000097722:Cohesins
chemical_list: D000076246:CCCTC-Binding Factor; D018797:Cell Cycle Proteins; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004250:DNA Topoisomerases, Type II; D004275:DNA, Ribosomal; D004268:DNA-Binding Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D012097:Repressor Proteins; D000097722:Cohesins; C000619697:CTCF protein, human; C000619698:Ctcf protein, mouse; C000618814:TOP2B protein, human; C000618815:Top2b protein, mouse
keywords: BioID; CTCF; ChIP-exo; ChIP-seq; Cohesin; Comparative genomics; DNA supercoiling; Genome organization; Hi-C; Proteomics; Topoisomerase II beta; Topological associated domains