Ledgf/P75 Decreases Nucleosome Accessibility

Abstract

LEDGF/p75 is a chromatin-binding protein that has been tied to integration of HIV-1 cDNA into human chromosomes and reduction of cellular stress-induced apoptosis. While the structural basis for the binding of the N-terminal PWWP domain of LEDGF to chromatin has been detailed, the binding mechanism and effects of LEDGF binding to chromatin is still not well understood. Here we detail the effects of LEDGF binding to nucleosomes through ensemble and single-molecule FRET assays and report that LEDGF binding to nucleosomes decreases accessibility of nucleosomal DNA to transcription factors.