Genome-wide repression of eRNA and target gene loci by the ETV6-RUNX1 fusion in acute leukemia.

ABSTRACT: Approximately 20%-25% of childhood acute lymphoblastic leukemias carry the ETV6-RUNX1 (E/R) fusion gene, a fusion of two central hematopoietic transcription factors, ETV6 (TEL) and RUNX1 (AML1). Despite its prevalence, the exact genomic targets of E/R have remained elusive. We evaluated gene loci and enhancers targeted by E/R genome-wide in precursor B acute leukemia cells using global run-on sequencing (GRO-seq). We show that expression of the E/R fusion leads to widespread repression of RUNX1 motif-containing enhancers at its target gene loci. Moreover, multiple super-enhancers from the CD19⁺/CD20⁺-lineage were repressed, implicating a role in impediment of lineage commitment. In effect, the expression of several genes involved in B cell signaling and adhesion was d

SUBMITTER: Teppo S 

PROVIDER: S-EPMC5088590 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature