RUNX1-ETO and RUNX1-EVI1 Differentially Reprogram the Chromatin Landscape in t(8;21) and t(3;21) AML
Acute myeloid leukemia (AML) is a heterogeneous disease caused by mutations in transcriptional regulator genes, but how different mutant regulators shape the chromatin landscape is unclear. Here, we compared the transcriptional networks of two types of AML with chromosomal translocations of the RUNX...
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doaj-59b02bb370ca41848c0035227f7fd41d2020-11-24T21:24:36ZengElsevierCell Reports2211-12472017-05-011981654166810.1016/j.celrep.2017.05.005RUNX1-ETO and RUNX1-EVI1 Differentially Reprogram the Chromatin Landscape in t(8;21) and t(3;21) AMLJustin Loke0Salam A. Assi1Maria Rosaria Imperato2Anetta Ptasinska3Pierre Cauchy4Yura Grabovska5Natalia Martinez Soria6Manoj Raghavan7H. Ruud Delwel8Peter N. Cockerill9Olaf Heidenreich10Constanze Bonifer11Institute for Cancer and Genomic Sciences, College of Medicine and Dentistry, University of Birmingham, B15 2TT Birmingham, UKInstitute for Cancer and Genomic Sciences, College of Medicine and Dentistry, University of Birmingham, B15 2TT Birmingham, UKInstitute for Cancer and Genomic Sciences, College of Medicine and Dentistry, University of Birmingham, B15 2TT Birmingham, UKInstitute for Cancer and Genomic Sciences, College of Medicine and Dentistry, University of Birmingham, B15 2TT Birmingham, UKInstitute for Cancer and Genomic Sciences, College of Medicine and Dentistry, University of Birmingham, B15 2TT Birmingham, UKNorthern Institute for Cancer Research, University of Newcastle, Newcastle upon Tyne NE2 4HH, UKNorthern Institute for Cancer Research, University of Newcastle, Newcastle upon Tyne NE2 4HH, UKInstitute for Cancer and Genomic Sciences, College of Medicine and Dentistry, University of Birmingham, B15 2TT Birmingham, UKDepartment of Hematology, Erasmus University Medical Center, Dr. Molewaterplein 50, 3015 GE Rotterdam, the NetherlandsInstitute for Cancer and Genomic Sciences, College of Medicine and Dentistry, University of Birmingham, B15 2TT Birmingham, UKNorthern Institute for Cancer Research, University of Newcastle, Newcastle upon Tyne NE2 4HH, UKInstitute for Cancer and Genomic Sciences, College of Medicine and Dentistry, University of Birmingham, B15 2TT Birmingham, UKAcute myeloid leukemia (AML) is a heterogeneous disease caused by mutations in transcriptional regulator genes, but how different mutant regulators shape the chromatin landscape is unclear. Here, we compared the transcriptional networks of two types of AML with chromosomal translocations of the RUNX1 locus that fuse the RUNX1 DNA-binding domain to different regulators, the t(8;21) expressing RUNX1-ETO and the t(3;21) expressing RUNX1-EVI1. Despite containing the same DNA-binding domain, the two fusion proteins display distinct binding patterns, show differences in gene expression and chromatin landscape, and are dependent on different transcription factors. RUNX1-EVI1 directs a stem cell-like transcriptional network reliant on GATA2, whereas that of RUNX1-ETO-expressing cells is more mature and depends on RUNX1. However, both types of AML are dependent on the continuous expression of the fusion proteins. Our data provide a molecular explanation for the differences in clinical prognosis for these types of AML.http://www.sciencedirect.com/science/article/pii/S2211124717306113RUNX1-EVI1RUNX1-ETOepigenetic landscapechromatintranscriptional networkacute myeloid leukemia |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Justin Loke Salam A. Assi Maria Rosaria Imperato Anetta Ptasinska Pierre Cauchy Yura Grabovska Natalia Martinez Soria Manoj Raghavan H. Ruud Delwel Peter N. Cockerill Olaf Heidenreich Constanze Bonifer |
spellingShingle |
Justin Loke Salam A. Assi Maria Rosaria Imperato Anetta Ptasinska Pierre Cauchy Yura Grabovska Natalia Martinez Soria Manoj Raghavan H. Ruud Delwel Peter N. Cockerill Olaf Heidenreich Constanze Bonifer RUNX1-ETO and RUNX1-EVI1 Differentially Reprogram the Chromatin Landscape in t(8;21) and t(3;21) AML Cell Reports RUNX1-EVI1 RUNX1-ETO epigenetic landscape chromatin transcriptional network acute myeloid leukemia |
author_facet |
Justin Loke Salam A. Assi Maria Rosaria Imperato Anetta Ptasinska Pierre Cauchy Yura Grabovska Natalia Martinez Soria Manoj Raghavan H. Ruud Delwel Peter N. Cockerill Olaf Heidenreich Constanze Bonifer |
author_sort |
Justin Loke |
title |
RUNX1-ETO and RUNX1-EVI1 Differentially Reprogram the Chromatin Landscape in t(8;21) and t(3;21) AML |
title_short |
RUNX1-ETO and RUNX1-EVI1 Differentially Reprogram the Chromatin Landscape in t(8;21) and t(3;21) AML |
title_full |
RUNX1-ETO and RUNX1-EVI1 Differentially Reprogram the Chromatin Landscape in t(8;21) and t(3;21) AML |
title_fullStr |
RUNX1-ETO and RUNX1-EVI1 Differentially Reprogram the Chromatin Landscape in t(8;21) and t(3;21) AML |
title_full_unstemmed |
RUNX1-ETO and RUNX1-EVI1 Differentially Reprogram the Chromatin Landscape in t(8;21) and t(3;21) AML |
title_sort |
runx1-eto and runx1-evi1 differentially reprogram the chromatin landscape in t(8;21) and t(3;21) aml |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2017-05-01 |
description |
Acute myeloid leukemia (AML) is a heterogeneous disease caused by mutations in transcriptional regulator genes, but how different mutant regulators shape the chromatin landscape is unclear. Here, we compared the transcriptional networks of two types of AML with chromosomal translocations of the RUNX1 locus that fuse the RUNX1 DNA-binding domain to different regulators, the t(8;21) expressing RUNX1-ETO and the t(3;21) expressing RUNX1-EVI1. Despite containing the same DNA-binding domain, the two fusion proteins display distinct binding patterns, show differences in gene expression and chromatin landscape, and are dependent on different transcription factors. RUNX1-EVI1 directs a stem cell-like transcriptional network reliant on GATA2, whereas that of RUNX1-ETO-expressing cells is more mature and depends on RUNX1. However, both types of AML are dependent on the continuous expression of the fusion proteins. Our data provide a molecular explanation for the differences in clinical prognosis for these types of AML. |
topic |
RUNX1-EVI1 RUNX1-ETO epigenetic landscape chromatin transcriptional network acute myeloid leukemia |
url |
http://www.sciencedirect.com/science/article/pii/S2211124717306113 |
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