TY - JOUR T1 - An Erg driven transcriptional program controls B-lymphopoiesis JF - bioRxiv DO - 10.1101/861542 SP - 861542 AU - Ashley P. Ng AU - Hannah D. Coughlan AU - Soroor Hediyeh-zadeh AU - Kira Behrens AU - Timothy M. Johanson AU - Michael Sze Yuan Low AU - Charles C. Bell AU - Omer Gilan AU - Yih-Chih Chan AU - Andrew J. Kueh AU - Thomas Boudier AU - Ladina DiRago AU - Craig D. Hyland AU - Helen Ierino AU - Sandra Mifsud AU - Elizabeth Viney AU - Tracy Willson AU - Mark A. Dawson AU - Rhys S. Allan AU - Marco J. Herold AU - Kelly Rogers AU - David M Tarlinton AU - Gordon K. Smyth AU - Melissa J. Davis AU - Stephen L. Nutt AU - Warren S. Alexander Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/12/03/861542.abstract N2 - B-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. ER -