miR-191 modulates B-cell development and targets transcription factors E2A, Foxp1, and Egr1

被引：15

作者：

Blume, Jonas ^{[1
]}

Zietara, Natalia ^{[1
]}

Witzlau, Katrin ^{[1
]}

Liu, Yanshan ^{[2
]}

Sanchez, Oskar Ortiz ^{[3
]}

Puchalka, Jacek ^{[2
]}

Winter, Samantha J. ^{[5
]}

Kunze-Schumacher, Heike ^{[5
]}

Saran, Namita ^{[1
]}

Dueber, Sandra ^{[4
]}

Roy, Bishnudeo ^{[4
]}

Weiss, Siegfried ^{[1
,4
]}

Klein, Christoph ^{[2
]}

Wurst, Wolfgang ^{[3
,6
,7
,8
]}

Lyszkiewicz, Marcin ^{[1
,2
]}

Krueger, Andreas ^{[1
,5
]}

机构：

[1] Hannover Med Sch, Inst Immunol, Hannover, Germany

[2] Ludwig Maximilians Univ Munchen, Univ Hosp, Dr von Hauner Childrens Hosp, Dept Pediat, Munich, Germany

[3] Helmholtz Ctr Munich, Inst Dev Genet, Munich, Germany

[4] Helmholtz Ctr Infect Res HZI, Mol Immunol, Braunschweig, Germany

[5] Goethe Univ Frankfurt, Inst Mol Med, Frankfurt, Germany

[6] Tech Univ Munchen Weihenstephan, Neuherberg, Germany

[7] German Ctr Neurodegenerat Dis DZNE, Site Munich, Munich, Germany

[8] Munich Cluster Syst Neurol SyNergy, Munich, Germany

来源：

EUROPEAN JOURNAL OF IMMUNOLOGY | 2019年 / 49卷 / 01期

关键词：

B cells; Lymphocyte development; miRNA; miR-191; Transcriptional factors; GENE-EXPRESSION; DIFFERENTIATION; RECOMBINATION; PROTEINS; PROLIFERATION; BINDING; FAMILY; GROWTH; E47; RNA;

D O I：

10.1002/eji.201847660

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

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.

引用

页码：121 / 132

页数：12

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