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Microarray-based Identification of Individual HERV Loci Expression: Application to Biomarker Discovery in Prostate Cancer
13:19

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Published on: November 2, 2013

Microarray-based sketches of the HERV transcriptome landscape.

Philippe Pérot1, Nathalie Mugnier, Cécile Montgiraud

  • 1Joint Unit Hospices Civils de Lyon, bioMérieux, Cancer Biomarkers Research Group, Centre Hospitalier Lyon Sud, Lyon, France.

Plos One
|July 5, 2012
PubMed
Summary
This summary is machine-generated.

Human endogenous retroviruses (HERVs) are transcribed more than previously thought, with nearly a third of the HERV repertoire active. This study developed a new method to analyze HERV transcription across various tissues and cancer samples.

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Area of Science:

  • Genomics
  • Molecular Biology
  • Virology

Background:

  • Human endogenous retroviruses (HERVs) are remnants of ancient viral infections integrated into the human genome.
  • Their long terminal repeats (LTRs) contain regulatory sequences, but studying individual HERV locus expression is challenging due to genomic complexity.
  • Historically, HERVs were considered largely silent due to epigenetic control, except for a few known examples.

Purpose of the Study:

  • To develop a generic and optimal method for characterizing individual HERV loci expression by minimizing cross-hybridization.
  • To investigate the human endogenous retrovirus (HERV) transcriptome across normal and tumor samples on a large scale.
  • To explore the functional implications of HERV LTRs and their genomic context.

Main Methods:

  • Designed a custom microarray targeting 5,573 unique HERV loci using 25-mer probes to reduce cross-hybridization.
  • Analyzed a diverse sample set comprising 40 normal and 39 tumor tissues.
  • Utilized probes within U3 and U5 regions of LTRs to assign potential functions (promoter, polyA).

Main Results:

  • Approximately one-third of the HERV repertoire is actively transcribed.
  • HERV transcription exhibits tissue tropism, is sensitive to cellular differentiation state, and does not correlate with HERV family age.
  • Active LTRs are associated with higher cellular gene density and a distinct upstream genomic configuration compared to silent LTRs.

Conclusions:

  • A significant portion of the human endogenous retrovirus (HERV) repertoire is transcriptionally active, challenging previous assumptions of widespread silencing.
  • The study provides a robust methodology for large-scale HERV transcriptome analysis, enabling future research into HERV-host interactions.
  • Observations suggest adaptive strategies between viruses and hosts, with active HERV LTRs influencing the surrounding cellular gene environment.