Enhancer decommissioning by Snail1-induced competitive displacement of TCF7L2 and down-regulation of transcriptional activators results in EPHB2 silencing
Schnappauf O, Beyes S, Dertmann A, Freihen V, Frey P, Jägle S, Rose K, Michoel T, Grosschedl R, Hecht A.
Biochim Biophys Acta. online article
Epithelial-mesenchymal transitions (EMT) occur in development and disease. They are accompanied by massive changes in gene expression. Mechanistic explanations for EMT-associated transcriptional reprogramming are largely lacking. We now show that SNAIL1, the master regulator of EMT, turns off the expression of the epithelial tumor suppressor gene EPHB2 by decommissioning of a transcriptional enhancer. Enhancer inactivation results from SNAIL1-induced remodeling of the cellular transcription factor landscape. This leads to a loss of the transcriptional activators TCF7L2, FOXA1 and MYB from the EPHB2 enhancer. Our findings underscore the importance of transcriptional enhancers for gene regulation under physiological and pathological conditions.
