%0 Journal Article
%A Guerrero-Martínez, Jose A.
%A Ceballos-Chávez, María
%A Koehler, Florian
%A Peiró, Sandra
%A Reyes, Jose C.
%T TGFβ promotes widespread enhancer chromatin opening and operates on genomic regulatory domains
%D 2020
%U http://hdl.handle.net/10668/3679
%X 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.
%K Chromatin
%K Gene expression regulation
%K Genome
%K Transforming growth factor beta
%K Enhancer elements, genetic
%K Genome informatics
%K Transcriptional regulatory elements
%K Cromatina
%K Regulación de la expresión génica
%K Genoma
%K Factor de crecimiento transformador beta
%K Elementos de facilitación genéticos
%~