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

Journal article
Authors E. Sondergaard
A. Rauch
M. Michaut
N. Rapin
M. Rehn
A. S. Wilhelmson
Alessandro Camponeschi
M. S. Hasemann
F. O. Bagger
J. Jendholm
K. J. Knudsen
S. Mandrup
Inga-Lill Mårtensson
B. T. Porse
Published in Cell Reports
Volume 29
Issue 9
Pages 2756-2769.e6
ISSN 2211-1247
Publication year 2019
Published at Institute of Medicine, Department of Rheumatology and Inflammation Research
Pages 2756-2769.e6
Language en
Links dx.doi.org/10.1016/j.celrep.2019.10...
Keywords hematopoietic stem-cells, transcription factor erg, cis-regulatory, elements, 3d structure, locus, expression, pax5, alpha, rearrangements, proliferation, Cell Biology
Subject categories Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

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.

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