TY  - JOUR
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
Y1  - 2016/11/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 1468 
EP  - 1477 
DO  - 10.1101/gr.193649.115 
VL  - 26 
IS  - 11 
UR  - http://genome.cshlp.org/content/26/11/1468.abstract 
N2  - 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. 
ER  -