title: Featuring the nucleosome surface as a therapeutic target.
abstract: Chromatin is the major regulator of gene expression and genome maintenance. Proteins that bind the nucleosome, the repetitive unit of chromatin, and the histone H4 tail are critical to establishing chromatin architecture and phenotypic outcomes. Intriguingly, nucleosome-binding proteins (NBPs) and the H4 tail peptide compete for the same binding site at an acidic region on the nucleosome surface. Although the essential facts about the nucleosome were revealed 17 years ago, new insights into its atomic structure and molecular mechanisms are still emerging. Several complex nucleosome:NBP structures were recently revealed, characterizing the NBP-binding sites on the nucleosome surface. Here we discuss the potential of the nucleosome surface as a therapeutic target and the impact and development of exogenous nucleosome-binding molecules (eNBMs).
authors.affiliation: Laboratory of Molecular Pharmacology, Department of Pharmaceutical Sciences, School of Health Sciences, University of Brasilia, Brasilia, 70919-970, Brazil.
authors.forename: Isabel Torres Gomes
authors.initials: IT
authors.lastname: da Silva
authors.affiliation: Laboratório Nacional de Biociências, LNBio, CNPEM, Campinas, Brazil.
authors.forename: Paulo Sergio Lopes
authors.initials: PS
authors.lastname: de Oliveira
authors.affiliation: Laboratory of Molecular Pharmacology, Department of Pharmaceutical Sciences, School of Health Sciences, University of Brasilia, Brasilia, 70919-970, Brazil. Electronic address: gsantos@unb.br.
authors.forename: Guilherme Martins
authors.initials: GM
authors.lastname: Santos
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D006801:Humans; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D009707:Nucleosomes / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D057786:Peptidomimetics / Q000494:pharmacology; D011485:Protein Binding
chemical_list: D009707:Nucleosomes; D010455:Peptides; D057786:Peptidomimetics
keywords: acidic patch; binding protein; chromatin; nucleosome; structure; therapeutic target