Abstract
Understanding how histone variants affect chromatin structure is essential for understanding their role in gene regulation and chromatin maintenance in vivo. The basic unit of chromatin is a nucleosome, which consists of 146 base pairs of DNA wrapped around a histone octamer, made up of two of each of the four core histones-H2A, H2B, H3, H4. Often in cells, however, these canonical histones get exchanged for histone variants so that certain regions of the genome become enriched with non-wild-type histones. For example, histone variant H2A.Z has been found to replace canonical H2A near the transcription start site of active genes, suggesting that H2A.Z promotes gene transcription. Conversely, H2A.Z has also been associated with regions of silent chromatin. In general, the mechanism by which H2A.Z affects chromatin structure and kinetics is not understood. Here, we use optical tweezers to mechanically stretch individual nucleosome arrays and quantitatively compare the behavior of nucleosomes containing wild-type histones and nucleosomes in which histone H2A has been replaced with H2A.Z. We find that H2A.Z decreases the nucleosome inner-turn rewinding rate compared to wild-type H2A, promoting an open conformation. Our results reveal the affect of H2A.Z on nucleosome kinetics and on chromatin structure.
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