Transcriptomics

Dataset Information

4

P100 deficiency alone is insufficient for full activation of the alternative NF-κB pathway: TNF signaling cooperates with p52-RelB activation in the transcriptional regulation of the enpp2/autotaxin promoter


ABSTRACT: Background: Constitutive activation of the alternative NF-κB pathway leads to marginal zone B cell expansion and disorganized spleen microarchitecture. Furthermore, uncontrolled alternative NF-κB signaling results in the development and progression of cancer. We aimed here to learn about the mechanisms how does the constitutively active alternative NF-κB pathway exert its effects in these malignant processes. Methodology/Principal Findings: To explore the consequences of constitutive alternative NF-κB activation on genome-wide transcription, we compared gene expression profiles of wild-type and NF-kB2/p100-deficient (p100-/-) primary mouse embryonic fibroblasts (MEFs) and spleens. Microarray experiments revealed 73 differentially regulated genes in p100-/- vs. wild-type MEFs. Chromatin immunoprecipitation (ChIP) assays showed in p100-/- MEFs direct binding of RelB and p52 to the promoter of the enpp2 gene encoding Enpp2/Autotaxin, a protein with an important role in lymphocyte homing and cell migration. Gene ontology analysis revealed upregulation of genes with anti-apoptotic/proliferative activity (enpp2, serpina3g, traf1, rrad), chemotactic/locomotory activity (enpp2, ccl8), and lymphocyte homing activity (enpp2, cd34). Most importantly, biochemical analyses of MEFs and gene expression analyses of mice indicated a crosstalk between classical and alternative NF-κB pathways. Conclusions/Significance: The present results show that uncontrolled alternative NF-κB signaling is further enhanced by classical NF-κB activation, indicating that p100 deficiency alone is insufficient for full induction of a subset of genes by the alternative NF-κB pathway. cell type comparison (wt vs p100-/-) after genetic modification

ORGANISM(S): Mus musculus  

SUBMITTER: Agnes Lovas   Daniela Albrecht 

PROVIDER: E-GEOD-30317 | ArrayExpress | 2012-12-21

SECONDARY ACCESSION(S): GSE30317PRJNA143559

REPOSITORIES: GEO, ArrayExpress

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Publications

p100 Deficiency is insufficient for full activation of the alternative NF-κB pathway: TNF cooperates with p52-RelB in target gene transcription.

Lovas Agnes A   Weidemann Anja A   Albrecht Daniela D   Wiechert Lars L   Weih Debra D   Weih Falk F  

PloS one 20120806 8


BACKGROUND: Constitutive activation of the alternative NF-κB pathway leads to marginal zone B cell expansion and disorganized spleen microarchitecture. Furthermore, uncontrolled alternative NF-κB signaling may result in the development and progression of cancer. Here, we focused on the question how does the constitutive alternative NF-κB signaling exert its effects in these malignant processes. METHODOLOGY/PRINCIPAL FINDINGS: To explore the consequences of unrestricted alternative NF-κB activati  ...[more]

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