In vitro and in vivo characterisation of structure‐based nucleosome binding peptides

Abstract

The modulation of chromatin is orchestrated by Nucleosome Binding Proteins (NBPs). 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. Cellbased 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. Support or Funding Information This work has been supported by CNPq for KT,VF and IT fellowships, Fap‐DF grant number 04/2017 for GS, iNEXT grant number 6756, funded by the Horizon 2020 programme of the European Union, for HI.