RUNX1-ETO Depletion in t(8;21) AML Leads to C/EBPα- and AP-1-Mediated Alterations in Enhancer-Promoter Interaction.
CCAAT-Enhancer-Binding Proteins
/ genetics
Chromosomes, Human, Pair 21
/ genetics
Chromosomes, Human, Pair 8
/ genetics
Core Binding Factor Alpha 2 Subunit
/ genetics
Enhancer Elements, Genetic
Gene Deletion
Gene Expression Regulation, Leukemic
Humans
Leukemia, Myeloid, Acute
/ genetics
Oncogene Proteins, Fusion
/ genetics
Promoter Regions, Genetic
RUNX1 Translocation Partner 1 Protein
/ genetics
Transcription Factor AP-1
/ genetics
Translocation, Genetic
AP-1 signaling in acute myeloid leukemia
Promoter-Capture Hi-C
RUNX1-ETO
acute myeloid leukemia
chromatin programming
epigenetic regulation
integrated analysis of high-throughput data
promoter-enhancer interactions
transcription factors
transcriptional networks
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
17 Sep 2019
17 Sep 2019
Historique:
received:
31
10
2018
revised:
07
06
2019
accepted:
12
08
2019
entrez:
19
9
2019
pubmed:
19
9
2019
medline:
12
9
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31533028
pii: S2211-1247(19)31080-0
doi: 10.1016/j.celrep.2019.08.040
pmc: PMC6899442
pii:
doi:
Substances chimiques
CCAAT-Enhancer-Binding Proteins
0
CEBPA protein, human
0
Core Binding Factor Alpha 2 Subunit
0
Oncogene Proteins, Fusion
0
RUNX1 Translocation Partner 1 Protein
0
RUNX1 protein, human
0
RUNX1T1 protein, human
0
Transcription Factor AP-1
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3022-3031.e7Subventions
Organisme : Worldwide Cancer Research
ID : 12-1309
Pays : United Kingdom
Commentaires et corrections
Type : ErratumIn
Informations de copyright
Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.
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