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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
Jonas Blume 1 , Natalia Ziętara 1 , Katrin Witzlau 1 , Yanshan Liu 2 , Oskar Ortiz Sanchez 3 , Jacek Puchałka 2 , Samantha J Winter 4 , Heike Kunze-Schumacher 4 , Namita Saran 1 , Sandra Düber 5 , Bishnudeo Roy 5 , Siegfried Weiss 5 , Christoph Klein 2 , Wolfgang Wurst 6 , Marcin Łyszkiewicz 2 , Andreas Krueger 4
Jonas Blume 1 , Natalia Ziętara 1 , Katrin Witzlau 1 , Yanshan Liu 2 , Oskar Ortiz Sanchez 3 , Jacek Puchałka 2 , Samantha J Winter 4 , Heike Kunze-Schumacher 4 , Namita Saran 1 , Sandra Düber 5 , Bishnudeo Roy 5 , Siegfried Weiss 5 , Christoph Klein 2 , Wolfgang Wurst 6 , Marcin Łyszkiewicz 2 , Andreas Krueger 4
+ et al

[No authors listed]

Author information
  • 1 Institute of Immunology, Hannover Medical School, Hannover, Germany.
  • 2 Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Munich, Germany.
  • 3 Institute of Developmental Genetics, Helmholtz Centre Munich, Germany.
  • 4 Institute for Molecular Medicine, Goethe University Frankfurt, Frankfurt, Germany.
  • 5 Molecular Immunology, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany.
  • 6 Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.

摘要


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