Journal
NATURE COMMUNICATIONS
Volume 11, Issue 1, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-020-16828-y
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Funding
- C.R.B. Blackburn Scholarship
- Australian National Health and Medical Research Council
- Royal Australasian College of Physicians
- Independent Research Institutes Infrastructure Support Scheme Grant from the Australian National Health and Medical Research Council [361646]
- Australian Cancer Research Fund
- Victorian State Government Operational Infrastructure Support
- Maddie Riewoldt's Vision
- Leukemia and Lymphoma Society of America (LLS) [SCOR 7001-13]
- Australian Phenomics Network
- Australian Government through the National Collaborative Research Infrastructure Strategy Program
- [1113577]
- [1016647]
- [1054618]
- [1054925]
- [1060179]
- [1122783]
- [1186575]
- [1159658]
- [1060675]
- [1155342]
- [1058344]
- [1124081]
- [1156095]
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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.
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