An Erg-driven transcriptional program controls B cell lymphopoiesis

Ng, AP; Coughlan, HD; Hediyeh-Zadeh, S; Behrens, K; Johanson, TM; Low, MSY; Bell, CC; Gilan, O; Chan, YC; Kueh, AJ; Boudier, T; Feltham, R; Gabrielyan, A; DiRago, L; Hyland, CD; Ierino, H; Mifsud, S; Viney, E; Willson, T; Dawson, MA; Allan, RS; Herold, MJ; Rogers, K; Tarlinton, DM; Smyth, GK; Davis, MJ; Nutt, SL; Alexander, WS

Author(s): Ng, AP; Coughlan, HD; Hediyeh-Zadeh, S; Behrens, K; Johanson, TM; Low, MSY; Bell, CC; Gilan, O; Chan, YC; Kueh, AJ; Boudier, T; Feltham, R; Gabrielyan, A; DiRago, L; Hyland, CD; Ierino, H; Mifsud, S; Viney, E; Willson, T; Dawson, MA; Allan, RS; Herold, MJ; Rogers, K; Tarlinton, DM; Smyth, GK; Davis, MJ; Nutt, SL; Alexander, WS;
Details: Publication Year 2020-06-15,Volume 11,Issue #1,Page 3013
Journal Title: Nature Communications
Publication Type: Journal Article
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.
Publisher: NPG
Research Division(s): Inflammation; Immunology; Blood Cells And Blood Cancer; Bioinformatics; Advanced Technology And Biology
PubMed ID: 32541654
Publisher's Version: https://doi.org/10.1038/s41467-020-16828-y
NHMRC Grants: NHMRC/GNT1155342, NHMRC/GNT1156095, NHMRC/1124081, NHMRC/1113577, NHMRC/1016647, NHMRC/1054618, NHMRC/1054925, NHMRC/1060179, NHMRC/1124081, NHMRC/1058344, NHMRC/1060675, NHMRC/1122783,
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Creation Date: 2020-06-22 11:52:55

Last Modified: 2020-06-22 03:48:31