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Expression analysis of murine splenic B-cells after retroviral transduction with a constitutively active variant of IRF5 (IRF5-4D)

ABSTRACT: Genome-wide gene expression analysis of murine splenic B-cells following retroviral transduction with a constitutively active IRF5 (IRF5-4D)

ORGANISM(S): Mus musculus

PROVIDER: GSE51719 | GEO | 2014/09/24

SECONDARY ACCESSION(S): PRJNA224704

REPOSITORIES: GEO

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Expression analysis of murine splenic B-cells after retroviral transduction with a constitutively active variant of IRF5 (IRF5-4D)

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Project description:The transcription factor interferon regulatory factor 5 (IRF5) is upregulated in Hodgkin lymphoma (HL) and a key regulator of the aberrant transcriptome characteristic of this disease. Here we show that IRF5 upregulation in HL is driven by transcriptional activation of a normally dormant endogenous retroviral LOR1a long terminal repeat (LTR) upstream of IRF5. Specifically, through screening of RNA-seq libraries, we detected LTR-IRF5 chimeric transcripts in multiple HL cell lines but not in normal B-cell controls. In HL, the LTR was in an open and hypomethylated epigenetic state and we further show the LTR is the site of transcriptional initiation. Among HL cell lines, usage of the LTR promoter strongly correlates with overall levels of IRF5 mRNA and protein, indicating that LTR transcriptional awakening is a major contributor to IRF5 upregulation in HL. Taken together, oncogenic IRF5 overexpression in HL is the result of a specific LTR transcriptional activation. We propose that such LTR derepression is a distinct mechanism of oncogene activation (“onco-exaptation”) and that such a mechanism warrants further investigation in molecular and cancer research.

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Project description:Expression analysis of murine splenic B-cells after retroviral transduction with a constitutively active variant of IRF5 (IRF5-4D)

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