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Series GSE79899 Query DataSets for GSE79899
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
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.
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.
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
Submission date Apr 04, 2016
Last update date May 15, 2019
Contact name Joost Martens
Organization name Radboud University
Department Molecular Biology
Street address Geert Grooteplein 26
City Nijmegen
ZIP/Postal code 6525 GA
Country Netherlands
Platforms (2)
GPL10999 Illumina Genome Analyzer IIx (Homo sapiens)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (24)
BioProject PRJNA317349
SRA SRP072835

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Supplementary file Size Download File type/resource
GSE79899_RAW.tar 760.2 Mb (http)(custom) TAR (of BEDGRAPH, WIG)
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Raw data are available in SRA
Processed data provided as supplementary file

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