GSE256003 An endogenous retrovirus regulates tumor-specific expression of the immune transcriptional regulator SP140 [RNA-seq]

Contributors : Adam K Dziulko ; Holly Allen ; Edward B ChuongSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensSpeckled Protein 140 (SP140) is a chromatin reader with critical roles regulating immune cell transcriptional programs, and SP140 splice variants are associated with immune diseases including Crohn ’s disease, multiple sclerosis, and chronic lymphocytic leukemia. SP140 expression is currently thought to be restricted to immune cells. However, by analyzing human transcriptomic datasets from a wide range of normal and cancer cell types, we found recurrent cancer-specific expression of SP140, d riven by an alternative intronic promoter derived from an intronic endogenous retrovirus (ERV). The ERV belongs to the primate-specific LTR8B family. The ERV drives expression of multiple cancer-specific isoforms, including a nearly full-length isoform that retains all the functional domains of the full-length canonical isoform and is also localized within the nucleus, consistent with a role in chromatin regulation. In a fibrosarcoma cell line, silencing the cancer-specific ERV promoter of SP140 resulted in increased sensitivity to interferon-mediated cytotoxicity and dysregulation of multiple genes. Our findings implicate aberrant ERV-mediated SP140 expression as a novel mechanism contributing to immune gene dysregulation in a wide range of cancer cells.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research