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ERG Controls B Cell Development by Promoting Igh V-to-DJ Recombination

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B cell development depends 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 find that ERG-deficient B lineage cells exhibit an early developmental block at the pre-B cell stage and proliferate less. The cells fail to express the immunoglobulin heavy chain due to inefficient V-to-DJ recombination, and cells that undergo recombination display 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, depends on ERG. These findings show that ERG serves as a critical regulator of B cell development by ensuring efficient and balanced V-to-DJ recombination.

Original languageEnglish
JournalCell Reports
Volume29
Issue number9
Pages (from-to)2756-2769.e6
DOIs
Publication statusPublished - 26 Nov 2019

    Research areas

  • B cell development, ERG, ETS-related gene, immunoglobulin heavy-chain gene, pre-BCR, transcriptional control, V(D)J recombination

ID: 58519830