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| Status |
Public on Jan 24, 2017 |
| Title |
The MLL-AF9 and MLL-AF4 oncofusion proteins bind a distinct enhancer repertoire and target the RUNX1 program in MLLr AML |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Other
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| Summary |
In MLL-rearranged (MLLr) leukemias the N terminal part of the MLL gene can be fused to over 60 different partner genes. Here, we investigate the genome wide binding of the MLL-AF9 and MLL-AF4 fusion proteins and their epigenetic signatures in order to define a core set of MLLr targets. We uncover both common as well as specific MLL-AF9 and MLL-AF4 target genes, which are all marked by H3K79me2, H3K27ac, and H3K4me3. Apart from promoter binding, we also identify MLL-AF9 and MLL-AF4 binding at specific subsets of non overlapping active distal regulatory elements. Despite this differential enhancer binding MLL-AF9 and MLL-AF4 still share a common gene program, which represents part of the RUNX1 gene program and constitutes of CD34+ and monocyte specific genes. Comparing these datasets revealed several zinc finger transcription factors as potential MLL-AF9 co-regulators. Together these results suggest that MLL-fusions collaborate with specific subsets of TFs to aberrantly regulate the RUNX1 gene program in 11q23 AMLs.
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| Overall design |
Genome-wide (ChIP-seq) binding of MLL, AF9, AF4, H3K4me3, H3K27ac, H3K79me2 and RUNX1 in THP-1 and MV4-11 AML cell lines. Expression Profiling (RNA-seq) of THP-1 and MV4-11 cell lines, as well as 5 MLL-AF9 positive patient blasts.
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| Contributor(s) |
Prange KM, Mandoli A, Kuznetsova T, Wang S, Sotoca AM, Marneth AE, van der Reijden BA, Stunnenberg HG, Martens JA |
| Citation(s) |
28114278 |
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| Submission date |
Apr 04, 2016 |
| Last update date |
Nov 11, 2021 |
| Contact name |
Joost Martens |
| E-mail(s) |
j.martens@science.ru.nl
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| Phone |
0243780645
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| Organization name |
Radboud University
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| Department |
RIMLS
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| Lab |
Molecular Biology
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| Street address |
Geert Grooteplein 28
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| City |
Nijmegen |
| State/province |
Nederland |
| ZIP/Postal code |
6525GA |
| Country |
Netherlands |
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| Platforms (2) |
| GPL10999 |
Illumina Genome Analyzer IIx (Homo sapiens) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (24)
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| Relations |
| BioProject |
PRJNA317349 |
| SRA |
SRP072835 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE79899_RAW.tar |
760.2 Mb |
(http)(custom) |
TAR (of BEDGRAPH, WIG) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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