AI Article Synopsis
- Chromatin plays a crucial role in how retroviruses, like HIV-1, integrate their genetic material into the host cell's genome, influenced by both histones and DNA structure.
- The study introduces a method using DNA minicircles (MCs) to mimic specific DNA distortions, allowing researchers to focus on the effects of these changes on integration efficiency and site selection.
- Results showed that integrating into MCs enhances HIV-1 integration and shows a preference for certain DNA structures, while also identifying unique properties for different retroviruses, helping to clarify the complex mechanisms behind retroviral integration.
Article Abstract
Chromatin regulates the selectivity of retroviral integration into the genome of infected cells. At the nucleosome level, both histones and DNA structure are involved in this regulation. We propose a strategy that allows to specifically study a single factor: the DNA distortion induced by the nucleosome. This strategy relies on mimicking this distortion using DNA minicircles (MCs) having a fixed rotational orientation of DNA curvature, coupled with atomic-resolution modeling. Contrasting MCs with linear DNA fragments having identical sequences enabled us to analyze the impact of DNA distortion on the efficiency and selectivity of integration. We observed a global enhancement of HIV-1 integration in MCs and an enrichment of integration sites in the outward-facing DNA major grooves. Both of these changes are favored by LEDGF/p75, revealing a new, histone-independent role of this integration cofactor. PFV integration is also enhanced in MCs, but is not associated with a periodic redistribution of integration sites, thus highlighting its distinct catalytic properties. MCs help to separate the roles of target DNA structure, histone modifications and integrase (IN) cofactors during retroviral integration and to reveal IN-specific regulation mechanisms.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5027509 | PMC |
| http://dx.doi.org/10.1093/nar/gkw651 | DOI Listing |
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