Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 49, Issue 1, Pages 121-132Publisher
WILEY
DOI: 10.1002/eji.201847660
Keywords
B cells; Lymphocyte development; miRNA; miR-191; Transcriptional factors
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Funding
- Braukmann-Wittenberg-Herz-Stiftung
- German Research Foundation (DFG)
- German Research Foundation [DFG SFB738-A7, SFB902-B15, EXC62, DFG LY150/1-1]
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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.
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