The effect of epigenetic modifications on the secondary structures and possible binding positions of the N-terminal tail of histone H3 in the nucleosome: a computational study

Abstract

The roles of histone tails as substrates for reversible chemical modifications and dynamic cognate surfaces for the binding of regulatory proteins are well established. Despite these crucial roles, experimentally derived knowledge of the structure and possible binding sites of histone tails in chromatin is limited. In this study, we utilized molecular dynamics of isolated histone H3 N-terminal peptides to investigate its structure as a function of post-translational modifications that are known to be associated with defined chromatin states. We observed a structural preference for α-helices in isoforms associated with an inactive chromatin state, while isoforms associated with active chromatin states lacked α-helical content. The physicochemical effect of the post-translational modifications was highlighted by the interaction of arginine side-chains with the phosphorylated serine residues in the inactive isoform. We also showed that the isoforms exhibit different tail lengths, and, using molecular docking of the first 15 N-terminal residues of an H3 isoform, identified potential binding sites between the superhelical gyres on the octamer surface, close to the site of DNA entry/exit in the nucleosome. We discuss the possible functional role of the binding of the H3 tail within the nucleosome on both nucleosome and chromatin structure and stability.Electronic supplementary materialThe online version of this article (doi:10.1007/s00894-017-3308-x) contains supplementary material, which is available to authorized users.

VRK1 and AURKB form a complex that cross inhibit their kinase activity and the phosphorylation of histone H3 in the progression of mitosis

“…Moreover, AURKB precedes haspin, since the activating phosphorylation of haspin by AURKB is necessary for the phosphorylation of H3T3 by haspin in mitosis [53]. An important issue that has not yet been properly addressed is the role played by the different H3 variants [59–61] in the sequential processes associated with the progression of mitosis. Most of the work on H3 phosphorylation has been studied independently of the H3 variant implicated, but the variant might be different for each kinase, something that will require further studies.…”

Sample Volume Reduction Using the Schwarzschild Objective for a Circular Dichroism Spectrophotometer and an Application to the Structural Analysis of Lysine-36 Trimethylated Histone H3 Protein

“…For example, it is assumed that H3K36me3 is linked to DNA repair in transcriptionally active regions, and it is thought the DNA repair processes involve drastic structural alterations of chromatin, namely complex of DNA and histone proteins, induced by the post-translational modifications of histones [ 21 , 22 , 26 , 27 ]. However, experimental and theoretical studies on the structural changes of histone, induced by modifications or DNA damage repair processes, are not so abundant [ 17 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ]. To precisely understand the mechanism of chromatin structural remodeling, cyclopedic studies of modification-induced structural changes of histones would be necessary.…”

The Effects of RNA.DNA-DNA Triple Helices on Nucleosome Structures and Dynamics

“…These regions are long, unstructured extensions which are key sites of multiple epigenetic markers. They are heavily charged, with four arginines and six lysines in the first 35 residues, and these extensions have been shown to influence nucleosome dynamics, DNA breathing, PTM accessibility, and e ector protein binding (28,(59)(60)(61)(62)(63)(64)(65)(66)(67). Visual inspection of the simulation trajectories showed a dramatic di erence in the H3 tail and entry DNA dynamics based on the presence or absence of RNA (Figures 3 and S7).…”