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

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 trigger...

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Hauptverfasser: Guerrero-Martínez, Jose Antonio (VerfasserIn) , Ceballos-Chávez, María (VerfasserIn) , Köhler, Florian (VerfasserIn) , Peiró, Sandra (VerfasserIn) , Reyes, Jose C. (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 03 December 2020
In: Nature Communications
Year: 2020, Jahrgang: 11, Pages: 1-20
ISSN:2041-1723
DOI:10.1038/s41467-020-19877-5
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/s41467-020-19877-5
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/s41467-020-19877-5
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Verfasserangaben:Jose A. Guerrero-Martínez, María Ceballos-Chávez, Florian Koehler, Sandra Peiró & Jose C. Reyes
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Zusammenfassung: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.
Beschreibung:Gesehen am 18.04.2022
Beschreibung:Online Resource
ISSN:2041-1723
DOI:10.1038/s41467-020-19877-5

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