Institute of Immunology, Hannover Medical School, Hannover, Germany.
Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Munich, Germany.
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.
miRNA 和转录调控网络在后转录基因调控中的相互依赖性在淋巴细胞发育中还了解甚少。在这里，我们鉴定出 miR-191 是包含转录因子 Foxp1、E2A 和 Egr1 的转录模块的直接上游调节剂。miR-191 的缺失和异位表达导致 B 细胞谱系细胞的发育停滞，表明 Foxp1、E2A 和 Egr1 的组合表达水平的精细调节，反过来控制体细胞重组和细胞因子驱动的扩增，是有效 B 细胞发育的前提。总之，我们提出 miR-191 通过精细调节关键的转录程序在 B 细胞发育中充当变阻器。
