ETS1 recruits cBAF to hijack the hematopoietic stem cell MYB enhancer in T-cell leukemia [dataset 1]

Notch signaling is the most prevalent oncogenic pathway in T-ALL, but clinical trials showed that pan-Notch inhibitors caused dose-limiting toxicities. Thus, we shifted our focus from Notch to ETS1, which is one of the top transcription factors that most frequently co-bind Notch-occupied regulatory elements in the T-ALL context. A top essential ETS1-dependent element was a Notch-bound enhancer at +140kb from MYB that we named the ETS-MYB enhancer (E-Me). Using genetically engineered mouse models and chromatin profiling, we showed that the E-Me selectively promotes self-renewal of hematopoietic stem cells, becomes inactive in committed T cell progenitors; and is reactivated to promote Notch-induced transformation. Overall design: ATAC-seq analysis of conventional T-ALL cell lines