Unravelling the Role of Linker Histone H1 and the H4-Tail in Chromatin (Un-)Folding
2016
Genomic DNA in eukaryotic cells is compacted into a structure called chromatin. The basic unit of chromatin is the nucleosome, which consists of 147 base pairs of DNA wrapped around a histone octamer protein. Arrays of nucleosomes fold into higher-order structures, enabling meters of DNA to be stored in a micrometer-sized cell nucleus. In order to resolve the spatial arrangement of nucleosomes in chromatin fibers, we studied the unfolding of nucleosome arrays by stretching with magnetic tweezers.The H4-tail domain is known to mediate contacts with the H2A histone of the adjacent nucleosome. Here, we also tested recombinant histones H4 and H2A with cysteine mutations to induce a covalent bond between nucleosomal units and to stabilize the fibers against unfolding. Under these conditions, we observed increased rupture forces upon stretching.Chromatin fibers assembled in the presence of linker histone H1 also featured increased stability and showed hysteresis in the force-extension curves. We quantified this non-equilibrium behavior using a novel statistical mechanics model that explicitly includes transition rates between successive states of unfolding. This detailed structural interpretation will help to elucidate the physics of chromatin folding and may have implications for our understanding of gene regulation in eukaryotes.
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