Epigenetic modifier drugs trigger widespread transcription of endogenous retroviruses
Dixie L Mager1,2, Matthew C Lorincz1
1Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
Nature Genetics
|June 29, 2017
Abstract:
A study in this issue demonstrates that epigenome-modifying drugs used in cancer chemotherapy induce transcription from thousands of previously unannotated transcription start sites, most of which are derived from ancient endogenous retroviruses (ERVs). This work, coupled with previous related findings, suggests that induction of ERVs, rather than direct effects on specific genes, may have a central role in the cellular responses to such agents and, in turn, their therapeutic efficacy.
Insights
Cancer chemotherapy drugs trigger ancient retroviruses (ERVs) to activate thousands of new transcription sites. This ERV activation, not direct gene effects, may drive cellular responses and therapeutic success.
Area of Science:
- Molecular Biology
- Cancer Research
- Genomics
Background:
- Epigenome-modifying drugs are utilized in cancer chemotherapy.
- The precise mechanisms underlying their therapeutic efficacy are not fully understood.
- Transcription start sites (TSS) are crucial regulatory elements in gene expression.
Purpose of the Study:
- To investigate the transcriptional consequences of epigenome-modifying chemotherapy agents.
- To identify novel transcription start sites (TSS) induced by these drugs.
- To explore the potential role of endogenous retroviruses (ERVs) in cellular response to chemotherapy.
Main Methods:
- Treatment of cells with epigenome-modifying drugs.
- High-throughput sequencing to profile transcription.
- Bioinformatic analysis to identify and annotate transcription start sites (TSS).
- Comparative analysis with known genomic elements, including endogenous retroviruses (ERVs).
Main Results:
- Epigenome-modifying drugs induced transcription from thousands of previously unannotated transcription start sites (TSS).
- A majority of these newly activated TSS were derived from ancient endogenous retroviruses (ERVs).
- This induction of ERV transcription was a prominent cellular response to the drugs.
Conclusions:
- The induction of endogenous retroviruses (ERVs) is a significant consequence of epigenome-modifying chemotherapy.
- ERV activation may play a central role in the cellular response to these agents.
- Understanding ERV induction could offer new insights into chemotherapy's therapeutic efficacy.
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