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Cell Rep. 2019 Nov 26;29(9):2756-2769.e6. doi: 10.1016/j.celrep.2019.10.098.

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

Author information

1
The Finsen Laboratory, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark; Biotech Research and Innovation Centre (BRIC), University of Copenhagen, 2200 Copenhagen N, Denmark; Danish Stem Cell Centre (DanStem) Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark.
2
Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense, Denmark.
3
The Finsen Laboratory, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark; Biotech Research and Innovation Centre (BRIC), University of Copenhagen, 2200 Copenhagen N, Denmark; Danish Stem Cell Centre (DanStem) Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark; The Bioinformatics Centre, Department of Biology, Faculty of Natural Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark.
4
Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden.
5
The Finsen Laboratory, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark; Biotech Research and Innovation Centre (BRIC), University of Copenhagen, 2200 Copenhagen N, Denmark; Danish Stem Cell Centre (DanStem) Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark. Electronic address: bo.porse@finsenlab.dk.

Abstract

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.

KEYWORDS:

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

PMID:
31775043
DOI:
10.1016/j.celrep.2019.10.098
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