Identification of common and distinct epigenetic re-programming properties of Core-Binding Factor (CBF) Fusion Proteins

Introduction: Leukaemia can be caused by translocations involving the transcription factor RUNX1 which results in the formation of CBF fusion proteins. The most common is RUNX1-ETO; a second is RUNX1-EVI1. Methods: We performed DNaseI-seq and RNA-seq in patients with CBF leukaemia. We used ChIP-seq to identify RUNX1 and CBF fusion protein binding sites. To identify which genes are directly responsive to RUNX1-EVI1, we measured mRNA and chromatin accessibility after knock down of RUNX1-EVI1 by siRNA. Results: We describe a distinct epigenetic landscape in each CBF leukaemia. We demonstrate that RUNX1 and RUNX1-EV…