In vitro, in vivo Characterization of Structure-Based Nucleosome Binding Peptides

Abstract

The modulation of chromatin is orchestrated by Nucleosome Binding Proteins (NBPs), although recent data show that lipids may have a significant influence over it. The nucleosome surface has been hypothesized as a therapeutic target due to its capacity to modulate chromatin architecture. Herein, we evaluated if Nucleosome Binding Peptides (NBPeps) would be able to occupy the nucleosome surface directly, thereby modulating chromatin status and influencing phenotypic outcomes. To understand how the nucleosome structure is affected by NBPeps, we performed biochemical assays indicating that distinct NBPeps present differential actions on the nucleosome structure despite binding to similar target regions on the nucleosome. Cell-based assays and animal models demonstrated that the NBPeps penetrate the cell and have specific effects on cell physiology and phenotypic outcome, suggesting that NBPeps might have important therapeutic implications.