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.
Keywords:
B cells; Lymphocyte development; Transcriptional factors; miR-191; miRNA.
© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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B-Lymphocytes / physiology*
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Basic Helix-Loop-Helix Transcription Factors / genetics
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Basic Helix-Loop-Helix Transcription Factors / metabolism*
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Cell Differentiation
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Cells, Cultured
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Early Growth Response Protein 1 / genetics
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Early Growth Response Protein 1 / metabolism*
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Forkhead Transcription Factors / genetics
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Forkhead Transcription Factors / metabolism*
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Gene Regulatory Networks
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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MicroRNAs / genetics*
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RNA, Small Interfering / genetics
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Recombination, Genetic
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Repressor Proteins / genetics
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Repressor Proteins / metabolism*
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Transcription, Genetic
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Transgenes / genetics
Substances
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Basic Helix-Loop-Helix Transcription Factors
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Early Growth Response Protein 1
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Egr1 protein, mouse
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Forkhead Transcription Factors
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Foxp1 protein, mouse
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MIRN191 microRNA, mouse
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MicroRNAs
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RNA, Small Interfering
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Repressor Proteins
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Tcf3 protein, mouse