Onco-exaptation of an endogenous retroviral LTR drives IRF5 expression in Hodgkin lymphoma

A. Babaian, M. T. Romanish, L. Gagnier, L. Y. Kuo, M. M. Karimi, C. Steidl, D. L. Mager

Research output: Contribution to journalArticle

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Abstract

The transcription factor interferon regulatory factor 5 (IRF5) is upregulated in Hodgkin lymphoma (HL) and is 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-sequencing 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.

Original languageEnglish
Pages (from-to)2542-2546
Number of pages5
JournalOncogene
Volume35
Issue number19
DOIs
Publication statusPublished - 12 May 2016
Externally publishedYes

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Interferon Regulatory Factors
Terminal Repeat Sequences
Hodgkin Disease
Transcriptional Activation
Up-Regulation
RNA Sequence Analysis
Cell Line
Oncogenes
Transcriptome
Epigenomics
B-Lymphocytes
Transcription Factors
Messenger RNA

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Babaian, A., Romanish, M. T., Gagnier, L., Kuo, L. Y., Karimi, M. M., Steidl, C., & Mager, D. L. (2016). Onco-exaptation of an endogenous retroviral LTR drives IRF5 expression in Hodgkin lymphoma. Oncogene, 35(19), 2542-2546. https://doi.org/10.1038/onc.2015.308

Onco-exaptation of an endogenous retroviral LTR drives IRF5 expression in Hodgkin lymphoma. / Babaian, A.; Romanish, M. T.; Gagnier, L.; Kuo, L. Y.; Karimi, M. M.; Steidl, C.; Mager, D. L.

In: Oncogene, Vol. 35, No. 19, 12.05.2016, p. 2542-2546.

Research output: Contribution to journalArticle

Babaian, A, Romanish, MT, Gagnier, L, Kuo, LY, Karimi, MM, Steidl, C & Mager, DL 2016, 'Onco-exaptation of an endogenous retroviral LTR drives IRF5 expression in Hodgkin lymphoma', Oncogene, vol. 35, no. 19, pp. 2542-2546. https://doi.org/10.1038/onc.2015.308
Babaian, A. ; Romanish, M. T. ; Gagnier, L. ; Kuo, L. Y. ; Karimi, M. M. ; Steidl, C. ; Mager, D. L. / Onco-exaptation of an endogenous retroviral LTR drives IRF5 expression in Hodgkin lymphoma. In: Oncogene. 2016 ; Vol. 35, No. 19. pp. 2542-2546.
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