Uuskula-Reimand, L;
Hou, H;
Samavarchi-Tehrani, P;
Rudan, MV;
Liang, M;
Medina-Rivera, A;
Mohammed, H;
... Wilson, MD; + view all
(2016)
Topoisomerase II beta interacts with cohesin and CTCF at topological domain borders.
Genome Biology
, 17
, Article 182. 10.1186/s13059-016-1043-8.
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Abstract
BACKGROUND: 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. RESULTS: 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. CONCLUSIONS: 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.
| Type: | Article |
|---|---|
| Title: | Topoisomerase II beta interacts with cohesin and CTCF at topological domain borders |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1186/s13059-016-1043-8 |
| Publisher version: | https://doi.org/10.1186/s13059-016-1043-8 |
| Language: | English |
| Additional information: | © The Author(s). 2016 This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Biotechnology & Applied Microbiology, Genetics & Heredity, Topoisomerase II beta, CTCF, Cohesin, BioID, ChIP-seq, ChIP-exo, Hi-C, Comparative genomics, Proteomics, Topological associated domains, DNA supercoiling, Genome organization, Model-Based Analysis, DNA-Damage Response, Gene-Expression, Breast-Cancer, Chromatin Interactions, Affinity Purification, Protein Complexes, Tumor-Suppressor, Strand Breaks, Growth-Factor |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10038303 |
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