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...

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Published inKlinische Pädiatrie
Main Authors Loke, J, Ptasinska, A, Imperato, MR, Assi, SA, Cauchy, P, Cowell, I, Heidenreich, O, Raghavan, M, Delwel, R, Cockerill, PN, Bonifer, C
Format Conference Proceeding
LanguageEnglish
Published 02.05.2016
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Summary: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-EVI-1 compete for a substantial proportion of genomic sites, in a similar fashion as RUNX1 and RUNX1-ETO. Conclusion: The epigenetic landscape and CBF fusion protein binding in the two leukaemias differ, driven by differences in DNA binding of key transcription factors.
ISSN:0300-8630
1439-3824
DOI:10.1055/s-0036-1582520