title: Intasome architecture and chromatin density modulate retroviral integration into nucleosome.
abstract: BACKGROUND
  Retroviral integration depends on the interaction between intasomes, host chromatin and cellular targeting cofactors as LEDGF/p75 or BET proteins. Previous studies indicated that the retroviral integrase, by itself, may play a role in the local integration site selection within nucleosomal target DNA. We focused our study on this local association by analyzing the intrinsic properties of various retroviral intasomes to functionally accommodate different chromatin structures in the lack of other cofactors.
  
  
  RESULTS
  Using in vitro conditions allowing the efficient catalysis of full site integration without these cofactors, we show that distinct retroviral integrases are not equally affected by chromatin compactness. Indeed, while PFV and MLV integration reactions are favored into dense and stable nucleosomes, HIV-1 and ASV concerted integration reactions are preferred into poorly dense chromatin regions of our nucleosomal acceptor templates. Predicted nucleosome occupancy around integration sites identified in infected cells suggests the presence of a nucleosome at the MLV and HIV-1 integration sites surrounded by differently dense chromatin. Further analyses of the relationships between the in vitro integration site selectivity and the structure of the inserted DNA indicate that structural constraints within intasomes could account for their ability to accommodate nucleosomal DNA and could dictate their capability to bind nucleosomes functionally in these specific chromatin contexts.
  
  
  CONCLUSIONS
  Thus, both intasome architecture and compactness of the chromatin surrounding the targeted nucleosome appear important determinants of the retroviral integration site selectivity. This supports a mechanism involving a global targeting of the intasomes toward suitable chromatin regions followed by a local integration site selection modulated by the intrinsic structural constraints of the intasomes governing the target DNA bending and dictating their sensitivity toward suitable specific nucleosomal structures and density.
authors: Mohamed Salah
authors: MS
authors: Benleulmi
authors: Julien
authors: J
authors: Matysiak
authors: Daniel Rodrigo
authors: DR
authors: Henriquez
authors: Cédric
authors: C
authors: Vaillant
authors: Paul
authors: P
authors: Lesbats
authors: Christina
authors: C
authors: Calmels
authors: Monica
authors: M
authors: Naughtin
authors: Oscar
authors: O
authors: Leon
authors: Anna Marie
authors: AM
authors: Skalka
authors: Marc
authors: M
authors: Ruff
authors: Marc
authors: M
authors: Lavigne
authors: Marie-Line
authors: ML
authors: Andreola
authors: Vincent
authors: V
authors: Parissi
mesh_terms: D002843:Chromatin / Q000378:metabolism / Q000821:virology*; D004247:DNA / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D019426:Integrases / Q000378:metabolism; D009707:Nucleosomes / Q000378:metabolism / Q000821:virology*; D012190:Retroviridae / Q000502:physiology*; D016662:Virus Integration
chemical_list: D002843:Chromatin; D009707:Nucleosomes; D004247:DNA; D019426:Integrases