Structural Alterations in the Nucleosome upon H3 Tail-Truncation Reveals a Crucial Role for the H2A C Terminal Docking Domain in Nucleosome Destabilization

Abstract

The nucleosomal organization of eukaryotic chromatin offers a physical barrier to DNA access and also acts as a repository of epigenetic marks controlling chromosomal behavior during different periods of cell cycle. Post-translational modifications of histones play a key role in the regulation of gene access in eukaryotes. The majority of these modifications occur in the N-terminal extensions of the histone H3 in the form of methylation, acetylation or phosphorylation of amino acid residues. Here, we report on a total of 400 ns of all-atom molecular dynamics simulations of intact and tail-truncated nucleosomes and examine the effect of H3 tail truncation on nucleosome structure in atomic detail. During the intact nucleosome simulation one of the H3 tail domains showed propensity of alpha-helix formation. Upon truncation of the H3 tail containing the alpha-helical domain structural alterations occurred in the close by H2A(alpha)3 domain involving arginine residues and in the H2A C terminal docking domain suggesting a pathway for allosteric regulation of nucleosome stability. The relation between the present observations and corresponding experiments [1] is discussed.Reference:1. Ferreira et. al., Molecular and Cellular Biology 2007.