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Blume, Jonas; Zietara, Natalia; Witzlau, Katrin; Liu, Yanshan; Sanchez, Oskar Ortiz; Puchalka, Jacek; Winter, Samantha J.; Kunze-Schumacher, Heike; Saran, Namita; Dueber, Sandra; Roy, Bishnudeo; Weiss, Siegfried; Klein, Christoph; Wurst, Wolfgang; Lyszkiewicz, Marcin; Krüger, Andreas (2019): miR-191 modulates B-cell development and targets transcription factors E2A, Foxp1, and Egr1. In: European Journal of Immunology, Vol. 49, No. 1: pp. 121-132
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Abstract

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.