ERG controls B-cell development by promoting Igh V-to-DJ recombination [microarray]

B-cell development is dependent on the coordinated expression and cooperation of several transcription factors. Here, we show that the transcription factor ETS Related Gene (ERG) is crucial for normal B-cell development, and that its deletion results in a substantial loss of bone marrow B-cell progenitors and peripheral B-cells as well as a skewing of splenic B-cell populations. We found that ERG-deficient B-lineage cells exhibited an early developmental block, at the pre-B cell stage, and proliferated less. The cells failed to express the immunoglobulin heavy chain due to inefficient V-to-DJ recombination and cells that managed to undergo recombination displayed a strong bias against incorporation of distal V gene segments. Furthermore, antisense transcription at PAX5-activated intergenic repeat (PAIR) elements located in the distal region of the Igh locus was completely dependent on ERG. These findings identify ERG as a novel critical regulator of B-cell development by ensuring efficient and balanced V-to-DJ recombination. Microarray-based gene expression of FACS-sorted progenitor B-cells (Lin-, B220+, CD19+, CD93+ CD43+/lo) derived from Erg fl/fl (WT) and Erg fl/fl;CD2iCre (KO) mice. Three biological replicates were made for each genotype.