RT Journal
A1 Teppo, Susanna
A1 Laukkanen, Saara
A1 Liuksiala, Thomas
A1 Nordlund, Jessica
A1 Oittinen, Mikko
A1 Teittinen, Kaisa
A1 Grönroos, Toni
A1 St-Onge, Pascal
A1 Sinnett, Daniel
A1 Syvänen, Ann-Christine
A1 Nykter, Matti
A1 Viiri, Keijo
A1 Heinäniemi, Merja
A1 Lohi, Olli
T1 Genome-wide repression of eRNA and target gene loci by the ETV6-RUNX1 fusion in acute leukemia
JF Genome Research 
JO Genome Research 
YR 2016 
FD November 01 
VO 26 
IS 11 
SP 1468 
OP 1477 
DO 10.1101/gr.193649.115 
UL http://genome.cshlp.org/content/26/11/1468.abstract 
AB 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 down-regulated, and the repression depended on the wild-type DNA-binding Runt domain of RUNX1. We also identified a number of E/R-regulated annotated and de novo noncoding genes. The results provide a comprehensive genome-wide mapping between E/R-regulated key regulatory elements and genes in precursor B cell leukemia that disrupt normal B lymphopoiesis.