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Title: | An Erg-driven transcriptional program controls B cell lymphopoiesis. | Authors: | Alexander W.S.;Rogers K.;Tarlinton D.M.;Smyth G.K.;Davis M.J.;Nutt S.L.;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.;Feltham R.;Gabrielyan A.;DiRago L.;Hyland C.D.;Ierino H.;Mifsud S.;Viney E.;Willson T.;Dawson M.A.;Allan R.S.;Herold M.J. | Monash Health Department(s): | Haematology | Institution: | (Ng, Behrens, Kueh, DiRago, Hyland, Ierino, Mifsud, Viney, Willson, Herold, Alexander) Blood Cells and Blood Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia (Ng, Coughlan, Johanson, Low, Kueh, Boudier, Allan, Herold, Rogers, Smyth, Davis, Nutt, Alexander) Department of Medical Biology, The University of Melbourne, Parkville, VIC 3010, Australia (Coughlan, Hediyeh-zadeh, Smyth, Davis) Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia (Johanson, Low, Allan, Nutt) Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia (Low) Monash Haematology, Monash Hospital, Clayton, VIC 3004, Australia (Bell, Gilan, Chan, Dawson) Peter MacCallum Cancer Centre, Parkville, VIC 3000, Australia (Bell, Gilan, Chan, Dawson) Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC 3010, Australia (Boudier, Rogers) Advanced Technology and Biology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia (Feltham, Gabrielyan) Inflammation Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3010, Australia (Dawson) Centre for Cancer Research, The University of Melbourne, Parkville, VIC 3010, Australia (Tarlinton) Department of Immunology and Pathology, Monash University, Melbourne, VIC 3004, Australia | Issue Date: | 16-Sep-2020 | Copyright year: | 2020 | Publisher: | Nature Research | Place of publication: | United Kingdom | Publication information: | Nature Communications. 11 (1) (no pagination), 2020. Article Number: 3013. Date of Publication: 01 Dec 2020. | Journal: | Nature Communications | 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.Copyright © 2020, The Author(s). | DOI: | http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.1038/s41467-020-16828-y | PubMed URL: | 32541654 [http://www.ncbi.nlm.nih.gov/pubmed/?term=32541654] | ISSN: | 2041-1723 (electronic) | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/27169 | Type: | Article | Subjects: | B lymphocyte cell differentiation cell maturation gene expression gene regulatory network genetic complementation immunoglobulin gene lymphoid progenitor cell lymphopoiesis transcription regulation VDJ recombination B lymphocyte receptor CD19 antigen CD22 antigen CD3 antigen CD40 ligand CD79a antigen CD79b antigen cre recombinase DNA dependent protein kinase fibrinogen receptor immunoglobulin D immunoglobulin G1 immunoglobulin M interferon regulatory factor 4 interleukin 2 receptor alpha interleukin 4 interleukin 5 leukosialin lymphoid enhancer factor 1 Myc protein protein Myb RAG1 protein transcription factor 7 like 1 transcription factor ERG transcription factor PAX5 Bach2 protein Pou2af1 protein transcription factor Ebf1 vpreb2 protein CD4 antigen |
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