%0 Journal Article
%A Ptasinska, Anetta
%A Pickin, Anna
%A Assi, Salam A
%A Chin, Paulynn Suyin
%A Ames, Luke
%A Avellino, Roberto
%A Gröschel, Stefan
%A Delwel, Ruud
%A Cockerill, Peter N
%A Osborne, Cameron S
%A Bonifer, Constanze
%T RUNX1-ETO Depletion in t(8;21) AML Leads to C/EBPα- and AP-1-Mediated Alterations in Enhancer-Promoter Interaction.
%J Cell reports
%V 28
%N 12
%@ 2211-1247
%C [New York, NY]
%I Elsevier
%M DKFZ-2019-02779
%P 3022 - 3031.e7
%D 2019
%X Acute myeloid leukemia (AML) is associated with mutations in transcriptional and epigenetic regulator genes impairing myeloid differentiation. The t(8;21)(q22;q22) translocation generates the RUNX1-ETO fusion protein, which interferes with the hematopoietic master regulator RUNX1. We previously showed that the maintenance of t(8;21) AML is dependent on RUNX1-ETO expression. Its depletion causes extensive changes in transcription factor binding, as well as gene expression, and initiates myeloid differentiation. However, how these processes are connected within a gene regulatory network is unclear. To address this question, we performed Promoter-Capture Hi-C assays, with or without RUNX1-ETO depletion and assigned interacting cis-regulatory elements to their respective genes. To construct a RUNX1-ETO-dependent gene regulatory network maintaining AML, we integrated cis-regulatory element interactions with gene expression and transcription factor binding data. This analysis shows that RUNX1-ETO participates in cis-regulatory element interactions. However, differential interactions following RUNX1-ETO depletion are driven by alterations in the binding of RUNX1-ETO-regulated transcription factors.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:31533028
%R 10.1016/j.celrep.2019.08.040
%U https://inrepo02.dkfz.de/record/147918