RT Journal Article
T1 TGFβ promotes widespread enhancer chromatin opening and operates on genomic regulatory domains
A1 Guerrero-Martínez, Jose A.
A1 Ceballos-Chávez, María
A1 Koehler, Florian
A1 Peiró, Sandra
A1 Reyes, Jose C.
K1 Chromatin
K1 Gene expression regulation
K1 Genome
K1 Transforming growth factor beta
K1 Enhancer elements, genetic
K1 Genome informatics
K1 Transcriptional regulatory elements
K1 Cromatina
K1 Regulación de la expresión génica
K1 Genoma
K1 Factor de crecimiento transformador beta
K1 Elementos de facilitación genéticos
AB 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.
PB Springer Nature
YR 2020
FD 2020-12-03
LK http://hdl.handle.net/10668/3679
UL http://hdl.handle.net/10668/3679
LA en
NO Guerrero-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):6196
DS RISalud
RD Apr 5, 2025