An Erg-driven transcriptional program controls B cell lymphopoiesis

Ashley P. Ng, Hannah D. Coughlan, Soroor Hediyeh-zadeh, Kira Behrens, Timothy M. Johanson, Michael Sze Yuan Low, Charles C. Bell, Omer Gilan, Yih-Chih Chan, Andrew J. Kueh, Thomas Boudier, Rebecca Feltham, Anna Gabrielyan, Ladina DiRago, Craig D. Hyland, Helen Ierino, Sandra Mifsud, Elizabeth Viney, Tracy Willson, Mark A. DawsonRhys S. Allan, Marco J. Herold, Kelly Rogers, David M. Tarlinton, Gordon K. Smyth, Melissa J. Davis, Stephen L. Nutt, Warren S. Alexander

Research output: Contribution to journalArticleResearchpeer-review

2 Citations (Scopus)

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.

Original languageEnglish
Article number3013
Number of pages14
JournalNature Communications
Volume11
Issue number1
DOIs
Publication statusPublished - 15 Jun 2020

Cite this