RUNX1-ETO depletion in t(8;21) AML leads to C/EBPα- and AP-1-mediated alterations in enhancer-promoter interaction

Research output: Contribution to journalArticlepeer-review


  • Luke Ames
  • Roberto Avellino
  • Stephan Groeschel
  • Ruud Delwel
  • Cameron S Osborne
  • Conny Bonifer

Colleges, School and Institutes

External organisations

  • Erasmus University Medical Center
  • Weizmann Institute of Science Israel
  • Heidelberg University Hospital
  • King's College London


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.


Original languageEnglish
Pages (from-to)3022-3031.e7
Number of pages18
JournalCell Reports
Issue number12
Publication statusPublished - 17 Sep 2019


  • acute myeloid leukemia, RUNX1-ETO, promoter-enhancer interactions, Promoter-Capture Hi-C, transcriptional networks, chromatin programming, transcription factors, epigenetic regulation, integrated analysis of high-throughput data, AP-1 signaling in acute myeloid leukemia