TY  - JOUR
AU  - Ptasinska, Anetta
AU  - Pickin, Anna
AU  - Assi, Salam A
AU  - Chin, Paulynn Suyin
AU  - Ames, Luke
AU  - Avellino, Roberto
AU  - Gröschel, Stefan
AU  - Delwel, Ruud
AU  - Cockerill, Peter N
AU  - Osborne, Cameron S
AU  - Bonifer, Constanze
TI  - RUNX1-ETO Depletion in t(8;21) AML Leads to C/EBPα- and AP-1-Mediated Alterations in Enhancer-Promoter Interaction.
JO  - Cell reports
VL  - 28
IS  - 12
SN  - 2211-1247
CY  - [New York, NY]
PB  - Elsevier
M1  - DKFZ-2019-02779
SP  - 3022 - 3031.e7
PY  - 2019
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:31533028
DO  - DOI:10.1016/j.celrep.2019.08.040
UR  - https://inrepo02.dkfz.de/record/147918
ER  -