miR-191 modulates B-cell development and targets transcription factors E2A, Foxp1, and Egr1

Eur J Immunol. 2019 Jan;49(1):121-132. doi: 10.1002/eji.201847660. Epub 2018 Oct 22.


The interdependence of posttranscriptional gene regulation via miRNA and transcriptional regulatory networks in lymphocyte development is poorly understood. Here, we identified miR-191 as direct upstream modulator of a transcriptional module comprising the transcription factors Foxp1, E2A, and Egr1. Deletion as well as ectopic expression of miR-191 resulted in developmental arrest in B lineage cells, indicating that fine tuning of the combined expression levels of Foxp1, E2A, and Egr1, which in turn control somatic recombination and cytokine-driven expansion, constitutes a prerequisite for efficient B-cell development. In conclusion, we propose that miR-191 acts as a rheostat in B-cell development by fine tuning a key transcriptional program.

Keywords: B cells; Lymphocyte development; Transcriptional factors; miR-191; miRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / physiology*
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Cell Differentiation
  • Cells, Cultured
  • Early Growth Response Protein 1 / genetics
  • Early Growth Response Protein 1 / metabolism*
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism*
  • Gene Regulatory Networks
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • MicroRNAs / genetics*
  • RNA, Small Interfering / genetics
  • Recombination, Genetic
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Transcription, Genetic
  • Transgenes / genetics


  • Basic Helix-Loop-Helix Transcription Factors
  • Early Growth Response Protein 1
  • Egr1 protein, mouse
  • Forkhead Transcription Factors
  • Foxp1 protein, mouse
  • MIRN191 microRNA, mouse
  • MicroRNAs
  • RNA, Small Interfering
  • Repressor Proteins
  • Tcf3 protein, mouse