Abstract
Genomic DNA is packaged in chromatin, a dynamic fiber variable in size and compaction. In chromatin, repeating nucleosome units wrap 145-147 DNA basepairs around histone proteins. Genetic and epigenetic regulation of genes relies on structural transitions in chromatin which are driven by intra- and inter-nucleosome dynamics and modulated by chemical modifications of the unstructured terminal tails of histones. Here we demonstrate how the interplay between histone H3 and H2A tails control ample nucleosome breathing motions. We monitored large openings of two genomic nucleosomes, and only moderate breathing of an engineered nucleosome in atomistic molecular simulations amounting to 24 μs. Transitions between open and closed nucleosome conformations were mediated by the displacement and changes in compaction of the two histone tails. These motions involved changes in the DNA interaction profiles of clusters of epigenetic regulatory aminoacids in the tails. Removing the histone tails resulted in a large increase of the amplitude of nucleosome breathing but did not change the sequence dependent pattern of the motions. Histone tail modulated nucleosome breathing is a key mechanism of chromatin dynamics with important implications for epigenetic regulation.
Highlights
In eukaryotic cells, the DNA is packed into chromatin, a dynamic fiber structure made of arrays of nucleosomes
From extensive sampling of nucleosome dynamics in atomistic molecular simulations, we show that genomic nucleosomes breath more extensively than engineered ones and we describe how two histone tails cooperate
The highest structural flexibility we monitored in the linker DNA (L-DNA) arms and the histone tails (Fig 1), shown by the broader range of the number of contacts with DNA formed by the histone tails compared to the histone core (Table 1 and S1 Fig)
Summary
The DNA is packed into chromatin, a dynamic fiber structure made of arrays of nucleosomes. Histone tails interact with the DNA in a non-specific manner, protruding from the nucleosome superhelix and embracing the DNA. Their role in controlling the gene expression has been extensively analyzed [3,4,5]. Lysine acetylation in H3 [11] and H4 [12] mark open, actively transcribed regions of chromatin. These tails modulate chromatin structure by controlling both inter- and intra-nucleosome interactions
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