Function
The H4 histone is a core component used in the formation nucleosomes. After a nucleosome is formed, it then wraps and compacts its DNA into chromatin thus limiting DNA's accessibility to cellular processes which may require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. The main application that is being observed for the purpose of this presentation is the interactions that involve the histone H4. The research being presented focuses mainly on the N- terminal tail interactions of this histone. The N-terminal tails of core histones in a nucleosome core particle (NCP) aid in a multitude of functions such as structural stability, thermal stability, and the stimulation of transcription binding factors.
Importance
The N-terminal tail interactions of the H4 histone are crucial in order to correctly fold the nucleosomes into compact units that can be used to form chromatin fibers. This interaction occurs on the G14 to R19 or K16 to N25 residues that reside on the N-terminal tail of H4 and the acidic patch of the neighboring nucleosome. The tetra-acetylation of the H4 histone significantly increased the B-factor or electron density spacing on the outward regions of the DNAs in 7 -8 superhelical locations (SHL) in comparison to the inward regions, terminal regions, and regions near the dyad which were barely affected. The H4 – K16-acetylated nucleosome inhibited the formation of 30nm fibers and cross-fiber interactions thus displaying the its critical role in chromatin decompaction. Through biochemical analysis of acetylated nucleosome core particles (NCPs) that were prepared via native chemical ligation, it was revealed that cation-induced self-association was reduced by the tetra-acetylation of residues H4-K5, K8, K12, and K16.
Relevance
Through various observations, the scientists have presumed that the acetylation of the nucleosome itself is what regulates the decompaction of the higher-order chromatin structure, even in the absence of chromatin- associated factors. The B-factors of the acetylated NCP when compared to the unmodified NCP was significantly higher in comparison around the superhelical locations (SHL): -1.5 and +5.5 respectively. These differences suggest that H4 tetra-acetylation causes greater fluctuation of the atomic positions around these SHLs. This lead scientists to conclude that intra- and inter-nucleosomal interactions exist between DNA and the residues 1-16 or 1-20 of the H4 tail.
Structural highlights
Below are the various structural highlight of the H4-tetra-acetylated NCP:
displays in green the molecule B which is composed of residues 1-20 while the color yellow represents the molecule F which highlights residues 1-15.
displays the histones interaction sites, in black, that were affected by the H4 tetra-acetylation.
Superimposition of the 2 nucleosome core particles (NCPs), shown in blue.
References
Wakamori M, Fujii Y, Suka N, Shirouzu M, Sakamoto K, Umehara T, Yokoyama S. Intra- and inter-nucleosomal interactions of the histone H4 tail revealed with a human nucleosome core particle with genetically-incorporated H4 tetra-acetylation. Sci Rep. 2015 Nov 26;5:17204. doi: 10.1038/srep17204. PMID:26607036 doi:http://dx.doi.org/10.1038/srep17204[1]
