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Title: Topoisomerase IIα represses transcription by enforcing promoter-proximal pausing
Authors: Herrero-Ruiz, Andrés
Martínez-García, Pedro Manuel
Terrón-Bautista, José
Millán-Zambrano, Gonzalo
Lieberman, Jenna Ariel
Jimeno-González, Silvia
Cortés-Ledesma, Felipe
metadata.dc.contributor.authoraffiliation: [Herrero-Ruiz,A; Martínez-García,PM; Terrón-Bautista,J; Millán-Zambrano,G; Jimeno-González,S; Cortés-Ledesma,F] Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Universidad de Sevilla-CSIC-Universidad Pablo de Olavide, Sevilla, Spain. [Lieberman,JA] Lymphocyte Nuclear Biology, NIAMS, NIH, Bethesda, MD, USA. [Jimeno-González,S] Departamento de Genética, Universidad de Sevilla, Sevilla, Spain. [Herrero-Ruiz,A; Cortés-Ledesma,F] Topology and DNA Breaks Group, Spanish National Cancer Centre (CNIO), Madrid, Spain.
Keywords: DNA supercoiling;DNA topoisomerases;DNA topology;Gene expression;Promoter-proximal pausing;Transcription elongation;ADN-topoisomerasas;Expresión génica;Elongación de la transcripción genética
metadata.dc.subject.mesh: Medical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell Line::Cell Line, Transformed
Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Isomerases::DNA Topoisomerases::DNA Topoisomerases, Type II
Medical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::DNA::DNA, Circular::DNA, Superhelical
Medical Subject Headings::Anatomy::Cells::Epithelial Cells
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Genes, Immediate-Early
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Phenomena and Processes::Chemical Phenomena::Chemical Processes::Biochemical Processes::Protein Binding
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Nuclear Proteins::Proto-Oncogene Proteins c-fos
Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Nucleotidyltransferases::RNA Nucleotidyltransferases::DNA-Directed RNA Polymerases::RNA Polymerase II
Medical Subject Headings::Anatomy::Sense Organs::Eye::Retina::Retinal Pigment Epithelium
Medical Subject Headings::Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Pyrimidines::Pyrimidinones::Barbiturates::Thiobarbiturates
Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Topoisomerase Inhibitors::Topoisomerase II Inhibitors
Issue Date: 13-Apr-2021
Publisher: Cell Press
Citation: Herrero-Ruiz A, Martínez-García PM, Terrón-Bautista J, Millán-Zambrano G, Lieberman JA, Jimeno-González S, et al. Topoisomerase IIα represses transcription by enforcing promoter-proximal pausing. Cell Rep. 2021 Apr 13;35(2):108977
Abstract: Accumulation of topological stress in the form of DNA supercoiling is inherent to the advance of RNA polymerase II (Pol II) and needs to be resolved by DNA topoisomerases to sustain productive transcriptional elongation. Topoisomerases are therefore considered positive facilitators of transcription. Here, we show that, in contrast to this general assumption, human topoisomerase IIα (TOP2A) activity at promoters represses transcription of immediate early genes such as c-FOS, maintaining them under basal repressed conditions. Thus, TOP2A inhibition creates a particular topological context that results in rapid release from promoter-proximal pausing and transcriptional upregulation, which mimics the typical bursting behavior of these genes in response to physiological stimulus. We therefore describe the control of promoter-proximal pausing by TOP2A as a layer for the regulation of gene expression, which can act as a molecular switch to rapidly activate transcription, possibly by regulating the accumulation of DNA supercoiling at promoter regions.
metadata.dc.identifier.doi: 10.1016/j.celrep.2021.108977
ISSN: 2211-1247 (Online)
Appears in Collections:01- Artículos - CABIMER. Centro Andaluz de Biología Molecular

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