Genomics

Dataset Information

0

An Oncogenic Super-Enhancer Formed through Somatic Mutation of a Noncoding Intergenic Element


ABSTRACT: 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. ChIP-Seq for transcription factors and co-factors in T cell acute lymphoblastic leukemia cell lines

ORGANISM(S): Homo sapiens  

SUBMITTER: Stephen E Sallan   Alla Berezovskaya  Lewis B Silverman  Alejandro Gutierrez  Takaomi Sanda  Mignon L Loh  Stephen P Hunger  Richard A Young  Lars Anders  Jessica Reddy  Brian J Abraham  Lee N Lawton  A T Look  Adam D Durbin  Marc R Mansour 

PROVIDER: E-GEOD-59657 | ArrayExpress | 2014-11-13

SECONDARY ACCESSION(S): GSE59657SRP044701PRJNA255872

REPOSITORIES: GEO, ArrayExpress, ENA

Similar Datasets

2012-02-09 | E-GEOD-29180 | ArrayExpress
2011-01-26 | E-GEOD-26014 | ArrayExpress
2012-03-14 | E-GEOD-33850 | ArrayExpress
2012-07-09 | E-GEOD-39179 | ArrayExpress
2013-12-23 | E-GEOD-50622 | ArrayExpress
2014-12-15 | E-GEOD-64188 | ArrayExpress
2013-02-13 | E-GEOD-44286 | ArrayExpress
2013-01-02 | E-GEOD-42355 | ArrayExpress
2014-09-29 | E-GEOD-53998 | ArrayExpress
2015-12-18 | E-GEOD-76181 | ArrayExpress