Detalle de: Enhancers regulation by TGFβ

Enhancers are DNA sequences that contain multiple binding sites for sequence-specific transcription factors and are classically defined as elements able of activating distant basal promoters regardless of their distance and orientation relative to them. The human genome contains more than 1.000.000 of poorly characterized enhancers which constitute an important part of the non-coding genome. Most of the diseases and predispositions caused by mutations at enhancers are uncharacterized and their study constitutes one of the major challenges of human genetics. Therefore, understanding the mechanisms of enhancer function and regulation is of paramount importance from a basic and also from a biomedical translational point of view. During the period 2018-2020 we have mapped and catalogued all the enhancers in mouse epithelial mammary cells and have characterized their regulation by the growth factor TGFβ, a trigger of EMT in epithelial cells. We have recently published that TGFβ causes a fast and widespread increase in chromatin accessibility of about 80% of all enhancers, irrespective of whether they are activated, repressed or not regulated by TGFβ, thus dissociating the concepts of enhancer accessibility and activity. In addition, we showed that TGFβ-regulated genes often are clustered in TGFβ regulatory domains (TRD) (Guerrero-Martínez et al., 2020).