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GEO help: Mouse over screen elements for information. |
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| 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
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| 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.
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| Overall design |
ChIP-Seq for transcription factors and co-factors in T cell acute lymphoblastic leukemia cell lines
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| 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 |
| E-mail(s) |
young_computation@wi.mit.edu
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| Phone |
617-258-5219
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| Organization name |
Whitehead Institute for Biomedical Research
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| Lab |
Young Lab
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| Street address |
9 Cambridge Center
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| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02142 |
| Country |
USA |
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| Platforms (3) |
| GPL9115 |
Illumina Genome Analyzer II (Homo sapiens) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (20)
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| 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 |
| GSM1442004 |
Med1_ChipSeq 11252013_C2GUGACXX_3.TTAGGC |
| GSM1442005 |
ChIP:MYB_05-175_Jurkat_040314 04182014_C4JDGACXX_6.GCCAAT |
| GSM1442006 |
ChIP:MYB_ab45150_Jurkat_040314 04182014_C4JDGACXX_6.ACAGTG |
| GSM1442007 |
Input for ChIP:MYB_Jurkat_040314 04182014_C4JDGACXX_6.CAGATC |
| GSM1519634 |
ChIP:H3K27ac_ab4729_Jurkat4_091914 [lab: Look-DFCI] |
| GSM1519635 |
ChIP:MYB_ab45150_Jurkat1_091914 [lab: Look-DFCI] |
| GSM1519636 |
Input for ChIP:Jurkat4_091914 [lab: Look-DFCI] |
| GSM1519637 |
Input for ChIP:Jurkat1_091914 [lab: Look-DFCI] |
| GSM1519638 |
ChIP:H3K27ac_ab4729_Jurkat1_091914 [lab: Look-DFCI] |
| GSM1519639 |
ChIP:MYB_ab45150_Jurkat4_091914 [lab: Look-DFCI] |
| GSM1519640 |
Input for ChIP:Jurkat3_091914 [lab: Look-DFCI] |
| GSM1519641 |
ChIP:MYB_ab45150_Jurkat3_091914 [lab: Look-DFCI] |
| GSM1519642 |
ChIP:H3K27ac_ab4729_Jurkat3_091914 [lab: Look-DFCI] |
| GSM1519643 |
ChIP:vMYB_ab45150_MOLT3_062714 |
| GSM1519644 |
ChIP:H3K27ac_ab4729_MOLT3_062714 |
| GSM1519645 |
Input for ChIP:MOLT3_062714 |
| GSM1519646 |
ChIP:TAL1_sc12984_MOLT3_062714 |
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| Relations |
| BioProject |
PRJNA255872 |
| SRA |
SRP044701 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE59657_RAW.tar |
1.8 Gb |
(http)(custom) |
TAR (of WIG) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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