ERG Controls B Cell Development by Promoting Igh V-to-DJ Recombination
Summary: 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 pro...
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Format: | Article |
Language: | English |
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Elsevier
2019-11-01
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Series: | Cell Reports |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124719314317 |
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doaj-e74588edb6cf4153acf3b0d5b1490be8 |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Elisabeth Søndergaard Alexander Rauch Magali Michaut Nicolas Rapin Matilda Rehn Anna S. Wilhelmson Alessandro Camponeschi Marie S. Hasemann Frederik O. Bagger Johan Jendholm Kasper J. Knudsen Susanne Mandrup Inga-Lill Mårtensson Bo T. Porse |
spellingShingle |
Elisabeth Søndergaard Alexander Rauch Magali Michaut Nicolas Rapin Matilda Rehn Anna S. Wilhelmson Alessandro Camponeschi Marie S. Hasemann Frederik O. Bagger Johan Jendholm Kasper J. Knudsen Susanne Mandrup Inga-Lill Mårtensson Bo T. Porse ERG Controls B Cell Development by Promoting Igh V-to-DJ Recombination Cell Reports |
author_facet |
Elisabeth Søndergaard Alexander Rauch Magali Michaut Nicolas Rapin Matilda Rehn Anna S. Wilhelmson Alessandro Camponeschi Marie S. Hasemann Frederik O. Bagger Johan Jendholm Kasper J. Knudsen Susanne Mandrup Inga-Lill Mårtensson Bo T. Porse |
author_sort |
Elisabeth Søndergaard |
title |
ERG Controls B Cell Development by Promoting Igh V-to-DJ Recombination |
title_short |
ERG Controls B Cell Development by Promoting Igh V-to-DJ Recombination |
title_full |
ERG Controls B Cell Development by Promoting Igh V-to-DJ Recombination |
title_fullStr |
ERG Controls B Cell Development by Promoting Igh V-to-DJ Recombination |
title_full_unstemmed |
ERG Controls B Cell Development by Promoting Igh V-to-DJ Recombination |
title_sort |
erg controls b cell development by promoting igh v-to-dj recombination |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2019-11-01 |
description |
Summary: 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. : Søndergaard et al. demonstrate that ERG is a critical transcriptional regulator essential for B cell development. Loss of ERG leads to a marked reduction in V-to-DJ recombination at the Igh locus, precluding B cell progenitors from expressing the pre-B cell receptor, which is required for entering the final stages of B cell development. Keywords: ETS-related gene, ERG, B cell development, V(D)J recombination, pre-BCR, immunoglobulin heavy-chain gene, transcriptional control |
url |
http://www.sciencedirect.com/science/article/pii/S2211124719314317 |
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doaj-e74588edb6cf4153acf3b0d5b1490be82020-11-24T21:11:16ZengElsevierCell Reports2211-12472019-11-0129927562769.e6ERG Controls B Cell Development by Promoting Igh V-to-DJ RecombinationElisabeth Søndergaard0Alexander Rauch1Magali Michaut2Nicolas Rapin3Matilda Rehn4Anna S. Wilhelmson5Alessandro Camponeschi6Marie S. Hasemann7Frederik O. Bagger8Johan Jendholm9Kasper J. Knudsen10Susanne Mandrup11Inga-Lill Mårtensson12Bo T. Porse13The 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, DenmarkDepartment of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense, DenmarkThe 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, DenmarkThe 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, DenmarkThe 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, DenmarkThe 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, DenmarkDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, SwedenThe 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, DenmarkThe 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, DenmarkThe 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, DenmarkThe 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, DenmarkDepartment of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense, DenmarkDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, SwedenThe 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; Corresponding authorSummary: 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. : Søndergaard et al. demonstrate that ERG is a critical transcriptional regulator essential for B cell development. Loss of ERG leads to a marked reduction in V-to-DJ recombination at the Igh locus, precluding B cell progenitors from expressing the pre-B cell receptor, which is required for entering the final stages of B cell development. Keywords: ETS-related gene, ERG, B cell development, V(D)J recombination, pre-BCR, immunoglobulin heavy-chain gene, transcriptional controlhttp://www.sciencedirect.com/science/article/pii/S2211124719314317 |