Structures of human nucleosomes containing major histone H3 variants

Abstract

The nucleosome is the fundamental repeating unit of chromatin, via which genomic DNA is packaged into the nucleus in eukaryotes. In the nucleosome, two copies of each core histone, H2A, H2B, H3 and H4, form a histone octamer which wraps 146 base pairs of DNA around itself. All of the core histones except for histone H4 have nonallelic isoforms called histone variants. In humans, eight histone H3 variants, H3.1, H3.2, H3.3, H3T, H3.5, H3.X, H3.Y and CENP-A, have been reported to date. Previous studies have suggested that histone H3 variants possess distinct functions in the formation of specific chromosome regions and/or in the regulation of transcription and replication. H3.1, H3.2 and H3.3 are the most abundant H3 variants. Here, crystal structures of human nucleosomes containing either H3.2 or H3.3 have been solved. The structures were essentially the same as that of the H3.1 nucleosome. Since the amino-acid residues specific for H3.2 and H3.3 are located on the accessible surface of the H3/H4 tetramer, they may be potential interaction sites for H3.2- and H3.3-specific chaperones.

Structure of the CENP-A nucleosome and its implications for centromeric chromatin architecture

“…1), as in the canonical human H3 nucleosomes (Tsunaka et al, 2005;Tachiwana et al, 2010Tachiwana et al, , 2011bIwasaki et al, 2011). This is consistent with the octasome model for the CENP-A nucleosome.…”

DAXX co-folds with H3.3/H4 using high local stability conferred by the H3.3 variant recognition residues

“…Each horizontal bar represents an individual peptide from (H3.3/H4) 2 (B) or H3.3/H4/DAXX (C) and is color-coded for percent deuteration at each time point (10 1 , 10 2 , 10 3 , 10 4 and 10 5 s) by individual stripes within each bar. Peptides are placed beneath schematics of the secondary structural elements of H3.3 or H4 from the crystal structures of (H3.3/H4) 2 (B) [from the H3.3 nucleosome, PDB 3AV2; (27)] and H3.3/H4/DAXX (C) [PDB 4H9N; (15)], which are shown adjacent to the H/DX data from each respective complex. ( D–I ) Enlarged peptides from panel B (D–I, left) and panel C (D–I, right) are shown side-by-side.…”

Histone exchange, chromatin structure and the regulation of transcription

“…H3.3 differs from the canonical histone H3 in five amino acids that do not impart any considerable structural alteration to the nucleosomes 20 . The different amino acids contribute to the genomic localization of H3.3, as mutating these residues prevents the incorporation of the replication-independent H3.3 into nucleosomes 8 .…”