miR-191 modulates B-cell development and targets transcription factors E2A, Foxp1, and Egr1.
Eur J Immunol. 2018 Oct 3. doi: 10.1002/eji.201847660. [Epub ahead of print]
|Authors/Editors:||Blume J, Ziętara N, Witzlau K, Liu Y, Sanchez OO, Puchałka J, Winter SJ, Kunze-Schumacher H, Saran N, Düber S, Roy B, Weiss S, Klein C, Wurst W, Łyszkiewicz M, Krueger A.|
The interdependence of post-transcriptional 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.