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

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 show...

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Bibliographische Detailangaben
Hauptverfasser: Ptasinska, Anetta (VerfasserIn) , Gröschel, Stefan (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: November 5, 2019
In: Cell reports
Year: 2019, Jahrgang: 28, Heft: 12, Pages: 3022–3031, e1–e7
ISSN:2211-1247
DOI:10.1016/j.celrep.2019.08.040
Online-Zugang:Verlag, Volltext: https://doi.org/10.1016/j.celrep.2019.08.040
Verlag: http://www.sciencedirect.com/science/article/pii/S2211124719310800
Volltext
Verfasserangaben:Anetta Ptasinska, Anna Pickin, Salam A. Assi, Paulynn Suyin Chin, Luke Ames, Roberto Avellino, Stefan Gröschel, Ruud Delwel, Peter N. Cockerill, Cameron S. Osborne, and Constanze Bonifer
Beschreibung
Zusammenfassung: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.
Beschreibung:Im Titel wird alpha als griechischer Buchstabe dargestellt
Gesehen am 04.12.2019
Beschreibung:Online Resource
ISSN:2211-1247
DOI:10.1016/j.celrep.2019.08.040

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