SNAIL1-mediated downregulation of FOXA proteins facilitates the inactivation of transcriptional enhancer elements at key epithelial genes in colorectal cancer cells
Jägle S, Busch H, Freihen V, Beyes S, Schrempp M, Boerries M, Hecht A.
PLoS Genet. 2017;13(11):e1007109.
Local invasion and dissemination of cancer cells are greatly facilitated by epithelial-mesenchymal transition (EMT). This process is accompanied by profound changes in gene expression and represents an extreme form of transcriptional reprogramming. Here we show that pervasive repression of epithelial genes to a large extent results from the downregulation of the FOXA family of pioneer transcription factors by the EMT-inducer SNAIL1. FOXA factors actively shape the enhancer landscape in epithelial cells. Accordingly, loss of FOXA function leads to chromatin condensation and loss of enhancer activity at key epithelial genes.
