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MLV integration site selection is driven by a subset of strong enhancers and active promoters

Friday, November 08, 2013 — Poster Session III

10:00 a.m. – 12:00 p.m.

FAES Academic Center (Upper-Level Terrace)

NHGRI

GEN-18

Authors

  • MC LaFave
  • GK Varshney
  • DE Gildea
  • TG Wolfsberg
  • AD Baxevanis
  • SM Burgess

Abstract

Retroviruses integrate into the host genome in patterns specific to each virus. Understanding the causes of these patterns can provide insight into viral pathology and genome evolution, and is critical to the development of safe gene therapy vectors. We generated murine leukemia virus (MLV) integrations in human K562 cells and subjected them to second-generation sequencing. We developed a new analysis pipeline (the Genomic Integration Site Tracker, or GeIST), and used it to identify over 300,000 integration events. We analyzed the integrations in the context of ENCODE chromatin state data, and found that integrations were most highly enriched in a subset of strong enhancers and active promoters. Over 50% of the integrations were in 1.56% of the genome, well beyond the level expected based on previous studies. The integration pattern of MLV appears to be largely driven by regions that have high enrichment of multiple marks of active chromatin; this distinction is sufficient to explain why some strong enhancers were more prone to integration than others. The approach we employed is applicable to analyzing the integration pattern of any exogenous element, and could be a valuable preclinical screen to evaluate the safety of gene therapy vectors.

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