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An Erg driven transcriptional program controls B-lymphopoiesis

Ng, A. P.; Coughlan, H. D.; Hediyeh-zadeh, S.; Behrens, K.; Johanson, T. M.; Low, M. S. Y.; Bell, C. C.; Gilan, O.; Chan, Y.-C.; Kueh, A. J.; Boudier, T.; DiRago, L.; Hyland, C. D.; Ierino, H.; Mifsud, S.; Viney, E.; Willson, T.; Dawson, M. A.; Allan, R. S.; Herold, M. J.; Rogers, K.; Tarlinton, D. M.; Smyth, G.; Davis, M. J.; Nutt, S. L.; Alexander, W. S.

2019-12-03 immunology
10.1101/861542 bioRxiv
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Summary/AbstractB-cell development is initiated by the stepwise differentiation of hematopoietic stem cells into lineage committed progenitors, ultimately generating the mature B-cells that mediate protective immunity. This highly regulated process also generates clonal immunological diversity via recombination of immunoglobulin genes. 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 the earliest steps in B-cell differentiation. Erg initiates a transcriptional network involving the B-cell lineage defining genes, Ebf1 and Pax5, that directly promotes the expression of key genes involved in V(D)J recombination and formation of the B-cell receptor. Complementation of the Erg-deficiency with a productively rearranged immunoglobulin gene rescued B-cell development, demonstrating that Erg is an essential and exquisitely stage specific regulator of the gene regulatory network controlling B-lymphopoiesis.

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