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Title: TGFβ promotes widespread enhancer chromatin opening and operates on genomic regulatory domains
Authors: Guerrero-Martínez, Jose A.
Ceballos-Chávez, María
Koehler, Florian
Peiró, Sandra
Reyes, Jose C.
metadata.dc.contributor.authoraffiliation: [Guerrero-Martínez,JA; Ceballos-Chávez,M; Reyes,JC] Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Consejo Superior de Investigaciones Científicas-Universidad de Sevilla-Universidad Pablo de Olavide (CSIC-USE-UPO), Seville, Spain. [Koehler;F] Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, Heidelberg, Germany. [Koehler;F] Faculty of Biosciences, Heidelberg University, Heidelberg, Germany. [Peiró,S] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain.
Keywords: Chromatin;Gene expression regulation;Genome;Transforming growth factor beta;Enhancer elements, genetic;Genome informatics;Transcriptional regulatory elements;Cromatina;Regulación de la expresión génica;Genoma;Factor de crecimiento transformador beta;Elementos de facilitación genéticos
metadata.dc.subject.mesh: Medical Subject Headings::Organisms::Eukaryota::Animals
Medical Subject Headings::Anatomy::Cells::Cellular Structures::Intracellular Space::Cell Nucleus::Cell Nucleus Structures::Intranuclear Space::Chromosomes::Chromosome Structures::Chromatin
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome
Medical Subject Headings::Anatomy::Cells::Epithelial Cells::HEK293 Cells
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell Line::Cell Line, Tumor::MCF-7 Cells
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Multigene Family
Medical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, Messenger
Medical Subject Headings::Chemicals and Drugs::Biological Factors::Intercellular Signaling Peptides and Proteins::Transforming Growth Factors
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Gene Components::Regulatory Elements, Transcriptional::Enhancer Elements, Genetic
Issue Date: 3-Dec-2020
Publisher: Springer Nature
Citation: Guerrero-Martínez JA, Ceballos-Chávez M, Koehler F, Peiró S, Reyes JC. TGFβ promotes widespread enhancer chromatin opening and operates on genomic regulatory domains. Nat Commun. 2020 Dec 3;11(1):6196
Abstract: The Transforming Growth Factor-β (TGFβ) signaling pathway controls transcription by regulating enhancer activity. How TGFβ-regulated enhancers are selected and what chromatin changes are associated with TGFβ-dependent enhancers regulation are still unclear. Here we report that TGFβ treatment triggers fast and widespread increase in chromatin accessibility in about 80% of the enhancers of normal mouse mammary epithelial-gland cells, irrespective of whether they are activated, repressed or not regulated by TGFβ. This enhancer opening depends on both the canonical and non-canonical TGFβ pathways. Most TGFβ-regulated genes are located around enhancers regulated in the same way, often creating domains of several co-regulated genes that we term TGFβ regulatory domains (TRD). CRISPR-mediated inactivation of enhancers within TRDs impairs TGFβ-dependent regulation of all co-regulated genes, demonstrating that enhancer targeting is more promiscuous than previously anticipated. The area of TRD influence is restricted by topologically associating domains (TADs) borders, causing a bias towards co-regulation within TADs.
metadata.dc.identifier.doi: 10.1038/s41467-020-19877-5
ISSN: 2041-1723 (Online)
Appears in Collections:01- Artículos - CABIMER. Centro Andaluz de Biología Molecular

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