Journal Article

DZNE-2020-06734

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png miR-191 modulates B-cell development and targets transcription factors E2A, Foxp1, and Egr1.

Blume, J. ; Ziętara, N. ; Witzlau, K. ; Liu, Y. ; Sanchez, O. O. ; Puchałka, J. ; Winter, S. J. ; Kunze-Schumacher, H. ; Saran, N. ; Düber, S. ; Roy, B. ; Weiss, S. ; Klein, C. ; Wurst, W.DZNE* ; Łyszkiewicz, M. (Corresponding author) ; Krueger, A.

2019
Wiley-VCH Weinheim

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Please use a persistent id in citations: doi:10.1002/eji.201847660

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.

Keyword(s): Animals (MeSH) ; B-Lymphocytes: physiology (MeSH) ; Basic Helix-Loop-Helix Transcription Factors: genetics (MeSH) ; Basic Helix-Loop-Helix Transcription Factors: metabolism (MeSH) ; Cell Differentiation (MeSH) ; Cells, Cultured (MeSH) ; Early Growth Response Protein 1: genetics (MeSH) ; Early Growth Response Protein 1: metabolism (MeSH) ; Forkhead Transcription Factors: genetics (MeSH) ; Forkhead Transcription Factors: metabolism (MeSH) ; Gene Regulatory Networks (MeSH) ; Mice (MeSH) ; Mice, Inbred C57BL (MeSH) ; Mice, Knockout (MeSH) ; MicroRNAs: genetics (MeSH) ; RNA, Small Interfering: genetics (MeSH) ; Recombination, Genetic (MeSH) ; Repressor Proteins: genetics (MeSH) ; Repressor Proteins: metabolism (MeSH) ; Transcription, Genetic (MeSH) ; Transgenes: genetics (MeSH) ; Basic Helix-Loop-Helix Transcription Factors ; Early Growth Response Protein 1 ; Egr1 protein, mouse ; Forkhead Transcription Factors ; Foxp1 protein, mouse ; MIRN191 microRNA, mouse ; MicroRNAs ; RNA, Small Interfering ; Repressor Proteins ; Tcf3 protein, mouse

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Contributing Institute(s):

1. Genome Engineering (AG Wurst)

Research Program(s):

1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)

Appears in the scientific report 2019

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; IF >= 5 ; JCR ; Nationallizenz ; SCOPUS ; Web of Science Core Collection

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