miR290-5p/292-5p activate the immunoglobulin kappa locus in B cell development

Autor: Jamie G. Bates, Hector Nolla, Patty B. Garcia, Mark S. Schlissel, Amie Cai
Jazyk: angličtina
Rok vydání: 2012
Předmět:
B Cells
Transcription
Genetic
Abelson murine leukemia virus
Cellular differentiation
Gene Expression
lcsh:Medicine
Biochemistry
Piperazines
Mice
Bone Marrow
Nucleic Acids
Molecular Cell Biology
Basic Helix-Loop-Helix Transcription Factors
Genetics of the Immune System
lcsh:Science
Regulation of gene expression
B-Lymphocytes
Gene knockdown
Multidisciplinary
biology
NF-kappa B
Cell Differentiation
Immunoglobulin kappa locus
medicine.anatomical_structure
Gene Knockdown Techniques
Benzamides
Imatinib Mesylate
Research Article
Immune Cells
Immunology
Recombination-activating gene
Immunoglobulin kappa-Chains
medicine
Animals
RNA
Messenger
Biology
B cell
lcsh:R
DNA
Cell Transformation
Viral
biology.organism_classification
Molecular biology
Introns
MicroRNAs
Pyrimidines
Imatinib mesylate
Gene Expression Regulation
Genetic Loci
Immune System
RNA
lcsh:Q
Developmental Biology
Zdroj: PLoS ONE, Vol 7, Iss 8, p e43805 (2012)
PLoS ONE
ISSN: 1932-6203
1000-4971
Popis: Regulated expression of miRNAs influences development in a wide variety of contexts. We report here that miR290-5p (100049710) and miR292-5p (100049711) are induced at the pre-B stage of murine B cell development and that they influence assembly of the Igκ light chain gene (243469) by contributing to the activation of germline Igκ transcription (κGT). We found that upon forced over-expression of miR290-5p/292-5p in Abelson Murine Leukemia Virus (AMuLV) transformed pro-B cells, two known activators of κGT, E2A (21423) and NF-κB (19697), show increased chromosomal binding to the kappa intronic enhancer. Conversely, knockdown of miR290-5p/292-5p in AMuLV pro-B cells blunts drug-induced activation of κGT. Furthermore, miR290-5p/292-5p knockdown also diminishes κGT activation, but not Rag1/2 (19373, 19374) expression, in an IL-7 dependent primary pro-B cell culture system. In addition, we identified a deficiency in κGT induction in miR290 cluster knockout mice. We hypothesize that increased expression of miR290-5p and miR292-5p contributes to the induction of κGT at the pre-B stage of B cell development through increased binding of NF-κB and E2A to kappa locus regulatory sequences.
Databáze: OpenAIRE
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