2022 Fiscal Year Annual Research Report
Characterizing the mechanism of chromatin remodeling by molecular dynamics simulations
| Project/Area Number |
20K06587
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | nucleosome / molecular dynamics / chromatin remodeling |
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| Outline of Annual Research Achievements |
In the last year, we analyzed our all-atom molecular dynamics (MD) simulations to reveal the details of the molecular mechanism of nucleosome sliding. We optimized the sliding pathway using the string method and computed the free energy change along the pathway. We found that DNA can move through the nucleosomes using small twist deformations that were also recently observed in chryo-electron microscopy images of nucleosomes in complex with chromatin remodelers. This shows that remodelers exploit the natural structural fluctuations of the nucleosome for their function.
Using our coarse-grained MD simulations, we studied the effect of DNA sequence on the energetics of the DNA deformations used by chromatin remodelers to slide the nucleosomal DNA using ATP. Using these results, we developed a powerful mathematical model that can predict the effect of DNA sequence on the sliding activity of chromatin remodelers in experiments. Our results explain how remodelers sense the DNA sequence of the underlying genome to create precise patterns of nucleosome positions that can serve specific biological functions, such as the regulation of gene expression.
Our results will soon be published in two peer-reviewed publications.
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