Histone tails cooperate to control the breathing of genomic nucleosomes

Genomic DNA is packaged in chromatin, a dynamic polymer that forms fibers variable in size and compaction. Chromatins monomeric unit, the nucleosome, is formed by wrapping [~] 146 basepairs of DNA around histone proteins. Dynamic transitions in the chromatin structure, which depend on intra- and inter-nucleosome dynamics and on chemical modifications of histones, are key to initiating gene regulation programs. The histone modifications occur in unstructured terminal regions known as tails and are key to epigenetic regulation of gene expression. Here we elucidate how the interplay between the tails of two histones, H3 and H2A modulate ample breathing motions of genomic nucleosomes. From 18 {micro}s of atomistic molecular dynamics simulations of two genomic and one engineered nucleosomes, we observed two rare, large opening events, one in each genomic nucleosome, and only small amplitude breathing in the engineered nucleosome. Clustering of the sampled structures revealed a strong correlation between DNA conformations with different degree of opening and histone tail conformations and positions. The ample nucleosome motions were caused by changes in the interaction profiles between the DNA and clusters of lysine and arginine residues in these tails, many of which are targets for epigenetic regulatory modifications. Given that histone tail modulated nucleosome breathing can change the structure and compaction of chromatin fibers, the mechanism we describe provides the basis for understanding chromatin dynamics at atomic resolution. Graphical TOC Entry O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=115 SRC="FIGDIR/small/282921v1_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@1f97a4eorg.highwire.dtl.DTLVardef@1cc97e5org.highwire.dtl.DTLVardef@1084cb8org.highwire.dtl.DTLVardef@1e5052f_HPS_FORMAT_FIGEXP M_FIG C_FIG