DNA minicircles clarify the specific role of DNA structure on retroviral integration
Langue
en
Article de revue
Ce document a été publié dans
2016-09-19, vol. 44, n° 16, p. 7830 - 7847
Oxford University Press
Résumé en anglais
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 ...Lire la suite >
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.< Réduire
Project ANR
Infrastructure Française pour la Biologie Structurale Intégrée - ANR-10-INBS-0005
Organisation et montée en puissance d'une Infrastructure Nationale de Génomique
Organisation et montée en puissance d'une Infrastructure Nationale de Génomique
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