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- Title
An Erg-driven transcriptional program controls B cell lymphopoiesis.
- Authors
Ng, Ashley P.; Coughlan, Hannah D.; Hediyeh-zadeh, Soroor; Behrens, Kira; Johanson, Timothy M.; Low, Michael Sze Yuan; Bell, Charles C.; Gilan, Omer; Chan, Yih-Chih; Kueh, Andrew J.; Boudier, Thomas; Feltham, Rebecca; Gabrielyan, Anna; DiRago, Ladina; Hyland, Craig D.; Ierino, Helen; Mifsud, Sandra; Viney, Elizabeth; Willson, Tracy; Dawson, Mark A.
- Abstract
B lymphoid development is initiated by the differentiation of hematopoietic stem cells into lineage committed progenitors, ultimately generating mature B cells. This highly regulated process generates clonal immunological diversity via recombination of immunoglobulin V, D and J gene segments. While several transcription factors that control B cell development and V(D)J recombination have been defined, how these processes are initiated and coordinated into a precise regulatory network remains poorly understood. Here, we show that the transcription factor ETS Related Gene (Erg) is essential for early B lymphoid differentiation. Erg initiates a transcriptional network involving the B cell lineage defining genes, Ebf1 and Pax5, which directly promotes expression of key genes involved in V(D)J recombination and formation of the B cell receptor. Complementation of Erg deficiency with a productively rearranged immunoglobulin gene rescued B lineage development, demonstrating that Erg is an essential and stage-specific regulator of the gene regulatory network controlling B lymphopoiesis. B cell development is tightly regulated in a stepwise manner to ensure proper generation of repertoire diversity via somatic gene rearrangements. Here, the authors show that a transcription factor, Erg, functions at the earliest stage to critically control two downstream factors, Ebf1 and Pax5, for modulating this gene rearrangement process.
- Subjects
B cells; T cell receptors; B cell receptors; GENE regulatory networks; IMMUNOGLOBULIN genes; GENE rearrangement
- Publication
Nature Communications, 2020, Vol 11, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-020-16828-y