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Global long terminal repeat activation participates in establishing the unique gene expression programme of classical Hodgkin lymphoma

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Item Type:Article
Title:Global long terminal repeat activation participates in establishing the unique gene expression programme of classical Hodgkin lymphoma
Creators Name:Edginton-White, B. and Cauchy, P. and Assi, S.A. and Hartmann, S. and Riggs, A.G. and Mathas, S. and Cockerill, P.N. and Bonifer, C.
Abstract:Long terminal repeat (LTR) elements are wide-spread in the human genome and have the potential to act as promoters and enhancers. Their expression is therefore under tight epigenetic control. We previously reported in classical Hodgkin Lymphoma (cHL) that a member of the THE1B class of LTR elements acted as a promoter for the proto-oncogene and growth factor receptor gene CSF1R and that expression of this gene is required for cHL tumour survival. However, to which extent and how such elements participate in globally shaping the unique cHL gene expression programme is unknown. To address this question we mapped the genome-wide activation of THE1-LTRs in cHL cells using a targeted next generation sequencing approach (RACE-Seq). Integration of these data with global gene expression data from cHL and control B cell lines showed a unique pattern of LTR activation impacting on gene expression, including genes associated with the cHL phenotype. We also show that global LTR activation is induced by strong inflammatory stimuli. Together these results demonstrate that LTR activation provides an additional layer of gene deregulation in classical Hodgkin lymphoma and highlight the potential impact of genome-wide LTR activation in other inflammatory diseases.
Keywords:Gene Expression Profiling, Genetic Promoter Regions, Hodgkin Disease, Human Genome, Neoplastic Gene Expression Regulation, Nucleic Acid Regulatory Sequences, Terminal Repeat Sequences, Transcriptional Activation, Tumor Biomarkers, Cultured Tumor Cells
Source:Leukemia
ISSN:0887-6924
Publisher:Nature Publishing Group
Volume:33
Number:6
Page Range:1463-1474
Date:June 2019
Official Publication:https://doi.org/10.1038/s41375-018-0311-x
PubMed:View item in PubMed

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