| Autor: |
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 |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
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| Zdroj: |
Cell Reports, Vol 29, Iss 9, Pp 2756-2769.e6 (2019) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2019.10.098 |
| Popis: |
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 |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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