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: | , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
03 December 2020
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| 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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| 520 | |a 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. | ||
| 650 | 4 | |a Chromatin | |
| 650 | 4 | |a Genome informatics | |
| 650 | 4 | |a Transcription | |
| 650 | 4 | |a Transcriptional regulatory elements | |
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