TY  - JOUR
AU  - Blume, Jonas
AU  - Ziętara, Natalia
AU  - Witzlau, Katrin
AU  - Liu, Yanshan
AU  - Sanchez, Oskar Ortiz
AU  - Puchałka, Jacek
AU  - Winter, Samantha J
AU  - Kunze-Schumacher, Heike
AU  - Saran, Namita
AU  - Düber, Sandra
AU  - Roy, Bishnudeo
AU  - Weiss, Siegfried
AU  - Klein, Christoph
AU  - Wurst, Wolfgang
AU  - Łyszkiewicz, Marcin
AU  - Krueger, Andreas
TI  - miR-191 modulates B-cell development and targets transcription factors E2A, Foxp1, and Egr1.
JO  - European journal of immunology
VL  - 49
IS  - 1
SN  - 0014-2980
CY  - Weinheim
PB  - Wiley-VCH
M1  - DZNE-2020-06734
SP  - 121-132
PY  - 2019
AB  - 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.
KW  - Animals
KW  - B-Lymphocytes: physiology
KW  - Basic Helix-Loop-Helix Transcription Factors: genetics
KW  - Basic Helix-Loop-Helix Transcription Factors: metabolism
KW  - Cell Differentiation
KW  - Cells, Cultured
KW  - Early Growth Response Protein 1: genetics
KW  - Early Growth Response Protein 1: metabolism
KW  - Forkhead Transcription Factors: genetics
KW  - Forkhead Transcription Factors: metabolism
KW  - Gene Regulatory Networks
KW  - Mice
KW  - Mice, Inbred C57BL
KW  - Mice, Knockout
KW  - MicroRNAs: genetics
KW  - RNA, Small Interfering: genetics
KW  - Recombination, Genetic
KW  - Repressor Proteins: genetics
KW  - Repressor Proteins: metabolism
KW  - Transcription, Genetic
KW  - Transgenes: genetics
KW  - Basic Helix-Loop-Helix Transcription Factors (NLM Chemicals)
KW  - Early Growth Response Protein 1 (NLM Chemicals)
KW  - Egr1 protein, mouse (NLM Chemicals)
KW  - Forkhead Transcription Factors (NLM Chemicals)
KW  - Foxp1 protein, mouse (NLM Chemicals)
KW  - MIRN191 microRNA, mouse (NLM Chemicals)
KW  - MicroRNAs (NLM Chemicals)
KW  - RNA, Small Interfering (NLM Chemicals)
KW  - Repressor Proteins (NLM Chemicals)
KW  - Tcf3 protein, mouse (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:30281154
DO  - DOI:10.1002/eji.201847660
UR  - https://pub.dzne.de/record/140412
ER  -