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Series GSE60130 Query DataSets for GSE60130
Status Public on Sep 24, 2014
Title Identification of a dynamic core transcriptional network in t(8;21) AML regulating differentiation block and self-renewal [ChIP-Seq]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary The leukemogenic fusion protein RUNX1/ETO impairs myeloid differentiation and drives malignant self-renewal. Here we use digital footprinting and ChIP-sequencing to identify the core RUNX1/ETO responsive transcriptional network of t(8;21) cells. We show that the transcriptional programme underlying leukemic propagation is regulated by a dynamic equilibrium between RUNX1/ETO and RUNX1 complexes, which bind in a mutually exclusive fashion to identical genomic sites. Perturbation of this equilibrium by RUNX1/ETO knockdown results in a global reassembly of transcription factor complexes within pre-existing open chromatin and the formation of a new C/EBP-alpha-dominated transcriptional network driving myeloid differentiation. Our work demonstrates that the block in myeloid differentiation in t(8;21) is caused by the dynamic balance between RUNX1/ETO and RUNX1 activities and the repression of C/EBP-alpha and highlights the core targets of epigenetic reprogramming in t(8;21) AML.
Overall design ChIP-sequencing and DNAse1-sequencing was used for the identification of a dynamic core transcriptional network in t(8;21) AML
Contributor(s) Ptasinska A, Assi SA, Piper J, Pickin A, Imperato MR, Hoogenkamp M, Cauchy P, Martinez-Soria N, James SR, Wu M, Ott S, Williamson D, Tenen DG, Westhead D, Cockerill P, Heidenreich O, Bonifer C
Citation(s) 25242324
Submission date Aug 05, 2014
Last update date May 15, 2019
Contact name Salam Adli Assi
Organization name University of Birmingham
Department Institute for Cancer and Genomic Sciences
Street address IBR
City Birmingham
ZIP/Postal code B15 2TT
Country United Kingdom
Platforms (2)
GPL10999 Illumina Genome Analyzer IIx (Homo sapiens)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (14)
GSM1466000 RUNX1_AMLblast_CD34_ChIPSeq
GSM1466001 DHS_siMM_Kasumi1_DNAseSeq
GSM1466002 DHS_siRE_Kasumi1_DNAseSeq
This SubSeries is part of SuperSeries:
GSE60131 Identification of a dynamic core transcriptional network in t(8;21) AML regulating differentiation block and self-renewal
BioProject PRJNA257531
SRA SRP045285

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Supplementary file Size Download File type/resource
GSE60130_RAW.tar 3.8 Gb (http)(custom) TAR (of BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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