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

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@article{27504345f1f04e279ca3f02bf0ecb233,
title = "ERG Controls B Cell Development by Promoting Igh V-to-DJ Recombination",
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, immunoglobulin heavy-chain gene, pre-BCR, transcriptional control, V(D)J recombination",
author = "Elisabeth S{\o}ndergaard and Alexander Rauch and Magali Michaut and Nicolas Rapin and Matilda Rehn and Wilhelmson, {Anna S} and Alessandro Camponeschi and Hasemann, {Marie S} and Bagger, {Frederik O} and Johan Jendholm and Knudsen, {Kasper J} and Susanne Mandrup and Inga-Lill M{\aa}rtensson and Porse, {Bo T}",
note = "Copyright {\circledC} 2019 The Author(s). Published by Elsevier Inc. All rights reserved.",
year = "2019",
month = "11",
day = "26",
doi = "10.1016/j.celrep.2019.10.098",
language = "English",
volume = "29",
pages = "2756--2769.e6",
journal = "Cell Reports",
publisher = "Cell Press",
number = "9",

}

RIS

TY - JOUR

T1 - ERG Controls B Cell Development by Promoting Igh V-to-DJ Recombination

AU - Søndergaard, Elisabeth

AU - Rauch, Alexander

AU - Michaut, Magali

AU - Rapin, Nicolas

AU - Rehn, Matilda

AU - Wilhelmson, Anna S

AU - Camponeschi, Alessandro

AU - Hasemann, Marie S

AU - Bagger, Frederik O

AU - Jendholm, Johan

AU - Knudsen, Kasper J

AU - Mandrup, Susanne

AU - Mårtensson, Inga-Lill

AU - Porse, Bo T

N1 - Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.

PY - 2019/11/26

Y1 - 2019/11/26

N2 - 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.

AB - 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.

KW - B cell development

KW - ERG

KW - ETS-related gene

KW - immunoglobulin heavy-chain gene

KW - pre-BCR

KW - transcriptional control

KW - V(D)J recombination

U2 - 10.1016/j.celrep.2019.10.098

DO - 10.1016/j.celrep.2019.10.098

M3 - Journal article

VL - 29

SP - 2756-2769.e6

JO - Cell Reports

JF - Cell Reports

IS - 9

ER -

ID: 58519830