ERG Controls B Cell Development by Promoting Igh V-to-DJ Recombination.
B cell development
ERG
ETS-related gene
V(D)J recombination
immunoglobulin heavy-chain gene
pre-BCR
transcriptional control
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
26 11 2019
26 11 2019
Historique:
received:
07
06
2019
revised:
28
08
2019
accepted:
24
10
2019
entrez:
28
11
2019
pubmed:
28
11
2019
medline:
21
10
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31775043
pii: S2211-1247(19)31431-7
doi: 10.1016/j.celrep.2019.10.098
pii:
doi:
Substances chimiques
ERG protein, human
0
Immunoglobulin Heavy Chains
0
Immunoglobulin Variable Region
0
Transcriptional Regulator ERG
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2756-2769.e6Informations de copyright
Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.