Guerrero-Martínez, Jose A.Ceballos-Chávez, MaríaKoehler, FlorianPeiró, SandraReyes, Jose C.2022-06-062022-06-062020-12-03Guerrero-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):6196http://hdl.handle.net/10668/3679The 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.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/ChromatinGene expression regulationGenomeTransforming growth factor betaEnhancer elements, geneticGenome informaticsTranscriptional regulatory elementsCromatinaRegulación de la expresión génicaGenomaFactor de crecimiento transformador betaElementos de facilitación genéticosMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Anatomy::Cells::Cellular Structures::Intracellular Space::Cell Nucleus::Cell Nucleus Structures::Intranuclear Space::Chromosomes::Chromosome Structures::ChromatinMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression RegulationMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::GenomeMedical Subject Headings::Anatomy::Cells::Epithelial Cells::HEK293 CellsMedical 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::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Multigene FamilyMedical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, MessengerMedical Subject Headings::Chemicals and Drugs::Biological Factors::Intercellular Signaling Peptides and Proteins::Transforming Growth FactorsMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Gene Components::Regulatory Elements, Transcriptional::Enhancer Elements, Geneticresearch article33273453Acceso abierto10.1038/s41467-020-19877-52041-1723PMC7713251