An Erg-driven transcriptional program controls B cell lymphopoiesis

Nat Commun. 2020 Jun 15;11(1):3013. doi: 10.1038/s41467-020-16828-y.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / metabolism*
  • Cell Differentiation / genetics*
  • Cell Lineage / genetics
  • Cells, Cultured
  • Gene Regulatory Networks / genetics
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / metabolism*
  • Lymphopoiesis / genetics*
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Oncogene Proteins / genetics*
  • Oncogene Proteins / metabolism
  • PAX5 Transcription Factor / genetics
  • PAX5 Transcription Factor / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription, Genetic*
  • Transcriptional Regulator ERG / genetics*
  • Transcriptional Regulator ERG / metabolism
  • V(D)J Recombination / genetics

Substances

  • ERG protein, mouse
  • Oncogene Proteins
  • PAX5 Transcription Factor
  • Transcription Factors
  • Transcriptional Regulator ERG