TGFβ promotes widespread enhancer chromatin opening and operates on genomic regulatory domains

• Verfasst von: Guerrero-Martínez, Jose Antonio [VerfasserIn]
• Verfasst von: Ceballos-Chávez, María [VerfasserIn]
• Verfasst von: Köhler, Florian [VerfasserIn]
• Verfasst von: Peiró, Sandra [VerfasserIn]
• Verfasst von: Reyes, Jose C. [VerfasserIn]
• Titel: TGFβ promotes widespread enhancer chromatin opening and operates on genomic regulatory domains
• Verf.angabe: Jose A. Guerrero-Martínez, María Ceballos-Chávez, Florian Koehler, Sandra Peiró & Jose C. Reyes
• E-Jahr: 2020
• Jahr: 03 December 2020
• Umfang: 20 S.
• Fussnoten: Gesehen am 18.04.2022
• Titel Quelle: Enthalten in: Nature Communications
• Ort Quelle: [London] : Nature Publishing Group UK, 2010
• Jahr Quelle: 2020
• Band/Heft Quelle: 11(2020), Artikel-ID 6196, Seite 1-20
• ISSN Quelle: 2041-1723
• DOI: doi:10.1038/s41467-020-19877-5
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Chromatin
• Sach-SW: Genome informatics
• Sach-SW: Transcription
• Sach-SW: Transcriptional regulatory elements
• K10plus-PPN: 1799710769

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.