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Series GSE59657 Query DataSets for GSE59657
Status Public on Nov 13, 2014
Title An Oncogenic Super-Enhancer Formed through Somatic Mutation of a Noncoding Intergenic Element
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary In many cancers, critical oncogenes are driven from large regulatory elements, called super-enhancers, which recruit much of the cell’s transcriptional apparatus and are defined by extensive H3K27 acetylation. We found that in T-cell acute lymphoblastic leukemia (T-ALL), somatic heterozygous mutations introduce MYB binding motifs in a precise noncoding site, which nucleate a super-enhancer upstream of the TAL1 oncogene. Further analysis of genome-wide binding identified MYB and its histone acetylase binding partner CBP as core components of the TAL1 complex and of the TAL1-mediated feed-forward auto-regulatory loop that drives T-ALL. Furthermore, MYB and CBP occupy endogenous MYB binding sites in the majority of super-enhancer sites found in T-ALL cells. Thus, our study reveals a new mechanism for the generation of super-enhancers in malignant cells involving the introduction of somatic indel mutations within non-coding sequences, which introduce aberrant binding sites for the MYB master transcription factor.
Overall design ChIP-Seq for transcription factors and co-factors in T cell acute lymphoblastic leukemia cell lines
Contributor(s) Mansour MR, Abraham BJ, Anders L, Berezovskaya A, Gutierrez A, Durbin AD, Lawton LN, Sallan SE, Silverman LB, Loh ML, Hunger SP, Sanda T, Reddy J, Young RA, Look AT
Citation(s) 25394790
Submission date Jul 22, 2014
Last update date May 15, 2019
Contact name Richard A Young
Phone 617-258-5219
Organization name Whitehead Institute for Biomedical Research
Lab Young Lab
Street address 9 Cambridge Center
City Cambridge
State/province MA
ZIP/Postal code 02142
Country USA
Platforms (3)
GPL9115 Illumina Genome Analyzer II (Homo sapiens)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (20)
GSM1442001 TAL1 ChIP-seq in HSPC rep1 05062009_427E3AAXX_B3
GSM1442002 TAL1 ChIP-seq in HSPC rep2 04102009_3139VAAXX_B1
GSM1442003 H3K27Ac ChIP RPMI-8402_ChipSeq 11132012_64WVDAAXX_4
BioProject PRJNA255872
SRA SRP044701

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Supplementary file Size Download File type/resource
GSE59657_RAW.tar 1.8 Gb (http)(custom) TAR (of WIG)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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