Nucleosome knetics regulates the binding timescales of
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Chromatin consists of nucleosomes bound to DNA in patterns correlated with DNA primary sequence (1–4). Current ‘nucleosome sequencing’ experiments indicate a great deal of heterogeneity of nucleosome positioning, with some regions of precise nucleosome occupancy and other regions that are apparently much less well ordered. The origin of nucleosome ‘positioning’ along DNA remains controversial: some researchers stress the role of the DNA-sequence-dependence of histone–DNA interactions (1–3), whereas others emphasize roles of other mechanisms to control positions of nucleosomes, notably ‘statistical’ positioning of nucleosomes (5–8).
Statistical positioning follows from the existence of ‘barriers’ to nucleosome formation, i.e. locations along DNA that nucleosomes are unable to occupy. For example, non-histone proteins bound strongly to a specific DNA site might sterically prevent nucleosomes from occupying that location. The correlations in nucleosome positions near such a barrier can generate spatial variations of nucleosome occupancy, but without the necessity of any intrinsic DNA-sequence-dependence of histone–DNA interactions (5). Statistical positioning near barriers has been suggested as the origin of nucleosome positioning patterns near transcription start sites (TSS) (6,7,9–11), but without mechanistic understanding of the origin of the barriers. However, all theoretical analyses of statistical positioning have been based on ‘thermal’ equilibration of nucleosome positions along DNA (12–14).
Statistical positioning follows from the existence of ‘barriers’ to nucleosome formation, i.e. locations along DNA that nucleosomes are unable to occupy. For example, non-histone proteins bound strongly to a specific DNA site might sterically prevent nucleosomes from occupying that location. The correlations in nucleosome positions near such a barrier can generate spatial variations of nucleosome occupancy, but without the necessity of any intrinsic DNA-sequence-dependence of histone–DNA interactions (5). Statistical positioning near barriers has been suggested as the origin of nucleosome positioning patterns near transcription start sites (TSS) (6,7,9–11), but without mechanistic understanding of the origin of the barriers. However, all theoretical analyses of statistical positioning have been based on ‘thermal’ equilibration of nucleosome positions along DNA (12–14).
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Our effector-free chromatin condensation mechanism suggests that epigenetic markers not only serve as information carriers but also can physi- cally affect interactions between the DNA molecules. 2772-Pos Board B149Nucleosome Kinetics Regulates the Binding Timescales of Non-Histone Proteins to DNA Sites Jyotsana J
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