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TGFÎ2 promotes widespread enhancer chromatin opening and operates on genomic regulatory domains by Guerrero-Martínez, Jose A.; Ceballos-Chávez, María; Koehler, Florian; Peiró, Sandra; Reyes, Jose C. is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

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## 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.

Who reads TGFÎ2 promotes widespread enhancer chromatin opening and operates on genomic regulatory domains?

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Author
Guerrero-Martínez, Jose A.; Ceballos-Chávez, María; Koehler, Florian; Peiró, Sandra; Reyes, Jose C.
Publisher
Nature Publishing Group; Springer Science and Business Media LLC; [London]: Nature Publishing Group, 2010-; Society for Mining, Metallurgy and Exploration Inc.; Research Square (ISSN 2041-1723)
Published
2020
Language
EN
Field
Biochemistry, Genetics and Molecular Biology (Life Sciences)

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