Martínez-García, Pedro ManuelGarcía-Torres, MiguelDivina, FedericoTerrón-Bautista, JoséDelgado-Sainz, IreneGómez-Vela, FranciscoCortés-Ledesma, Felipe2022-09-292022-09-292021-01-19Martínez-García PM, García-Torres M, Divina F, Terrón-Bautista J, Delgado-Sainz I, Gómez-Vela F, et al. Genome-wide prediction of topoisomerase IIβ binding by architectural factors and chromatin accessibility. PLoS Comput Biol. 2021 Jan 19;17(1):e1007814.http://hdl.handle.net/10668/4184DNA topoisomerase II-β (TOP2B) is fundamental to remove topological problems linked to DNA metabolism and 3D chromatin architecture, but its cut-and-reseal catalytic mechanism can accidentally cause DNA double-strand breaks (DSBs) that can seriously compromise genome integrity. Understanding the factors that determine the genome-wide distribution of TOP2B is therefore not only essential for a complete knowledge of genome dynamics and organization, but also for the implications of TOP2-induced DSBs in the origin of oncogenic translocations and other types of chromosomal rearrangements. Here, we conduct a machine-learning approach for the prediction of TOP2B binding using publicly available sequencing data. We achieve highly accurate predictions, with accessible chromatin and architectural factors being the most informative features. Strikingly, TOP2B is sufficiently explained by only three features: DNase I hypersensitivity, CTCF and cohesin binding, for which genome-wide data are widely available. Based on this, we develop a predictive model for TOP2B genome-wide binding that can be used across cell lines and species, and generate virtual probability tracks that accurately mirror experimental ChIP-seq data. Our results deepen our knowledge on how the accessibility and 3D organization of chromatin determine TOP2B function, and constitute a proof of principle regarding the in silico prediction of sequence-independent chromatin-binding factors.enAtribución 4.0 InternacionalAtribución 4.0 InternacionalAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/Machine learningChromatinType II DNA topoisomerasesThymocytesGenomeMCF7 cellsAprendizaje automáticoCromatinaADN-Topoisomerasas de tipo IITimocitosGenomaCélulas MCF-7Medical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Anatomy::Cells::Cells, CulturedMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::GenomeMedical Subject Headings::Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biology::Genetics::GenomicsMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell Line::Cell Line, Tumor::MCF-7 CellsMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::MiceMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Protein BindingMedical Subject Headings::Anatomy::Cells::ThymocytesMedical Subject Headings::Anatomy::Cells::Cellular Structures::Intracellular Space::Cell Nucleus::Cell Nucleus Structures::Intranuclear Space::Chromosomes::Chromosome Structures::ChromatinMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Isomerases::DNA Topoisomerases::DNA Topoisomerases, Type IIMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Theoretical::Models, Biological::Models, GeneticMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::DNA Damage::DNA Breaks::DNA Breaks, Double-StrandedMedical Subject Headings::Phenomena and Processes::Mathematical Concepts::ProbabilityMedical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell LineMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Esterases::Deoxyribonucleases::Endodeoxyribonucleases::Deoxyribonuclease Iresearch article33465072Acceso abierto10.1371/journal.pcbi.10078141553-7358PMC7845959