title: Secondary structures of the core histone N-terminal tails: their role in regulating chromatin structure.
abstract: The core histone N-terminal tails dissociate from their binding positions in nucleosomes at moderate salt concentrations, and appear unstructured in the crystal. This suggested that the tails contributed minimally to chromatin structure. However, in vitro studies have shown that the tails were involved in a range of intra- and inter-nucleosomal as well as inter-fibre contacts. The H4 tail, which is essential for chromatin compaction, was shown to contact an adjacent nucleosome in the crystal. Acetylation of H4K16 was shown to abolish the ability of a nucleosome array to fold into a 30 nm fibre. The application of secondary structure prediction software has suggested the presence of extended structured regions in the histone tails. Molecular Dynamics studies have further shown that sections of the H3 and H4 tails assumed α-helical and β-strand content that was enhanced by the presence of DNA, and that post-translational modifications of the tails had a major impact on these structures. Circular dichroism and NMR showed that the H3 and H4 tails exhibited significant α-helical content, that was increased by acetylation of the tail. There is thus strong evidence, both from biophysical and from computational approaches, that the core histones tails, particularly that of H3 and H4, are structured, and that these structures are influenced by post-translational modifications. This chapter reviews studies on the position, binding sites and secondary structures of the core histone tails, and discusses the possible role of the histone tail structures in the regulation of chromatin organization, and its impact on human disease.
authors.affiliation: Advanced Biomolecular Research Cluster, University of the Free State, 339, Bloemfontein, 9300, South Africa.
authors.forename: Louis L
authors.initials: LL
authors.lastname: du Preez
authors.forename: Hugh-G
authors.initials: HG
authors.lastname: Patterton
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
chemical_list: D002843:Chromatin; D006657:Histones; D004247:DNA