{"title":"Incorporating multiscale methylation effects into nucleosome-resolution chromatin models for simulating mesoscale fibers.","authors":"Zilong Li, Stephanie Portillo-Ledesma, Moshe Janani, Tamar Schlick","doi":"10.1063/5.0242199","DOIUrl":null,"url":null,"abstract":"<p><p>Histone modifications play a crucial role in regulating chromatin architecture and gene expression. Here we develop a multiscale model for incorporating methylation in our nucleosome-resolution physics-based chromatin model to investigate the mechanisms by which H3K9 and H3K27 trimethylation (H3K9me3 and H3K27me3) influence chromatin structure and gene regulation. We apply three types of energy terms for this purpose: short-range potentials are derived from all-atom molecular dynamics simulations of wildtype and methylated chromatosomes, which revealed subtle local changes; medium-range potentials are derived by incorporating contacts between HP1 and nucleosomes modified by H3K9me3, to incorporate experimental results of enhanced contacts for short chromatin fibers (12 nucleosomes); for long-range interactions we identify H3K9me3- and H3K27me3-associated contacts based on Hi-C maps with a machine learning approach. These combined multiscale effects can model methylation as a first approximation in our mesoscale chromatin model, and applications to gene systems offer new insights into the epigenetic regulation of genomes mediated by H3K9me3 and H3K27me3.</p>","PeriodicalId":15313,"journal":{"name":"Journal of Chemical Physics","volume":"162 9","pages":""},"PeriodicalIF":3.1000,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11888786/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Chemical Physics","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1063/5.0242199","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, PHYSICAL","Score":null,"Total":0}
引用次数: 0
Abstract
Histone modifications play a crucial role in regulating chromatin architecture and gene expression. Here we develop a multiscale model for incorporating methylation in our nucleosome-resolution physics-based chromatin model to investigate the mechanisms by which H3K9 and H3K27 trimethylation (H3K9me3 and H3K27me3) influence chromatin structure and gene regulation. We apply three types of energy terms for this purpose: short-range potentials are derived from all-atom molecular dynamics simulations of wildtype and methylated chromatosomes, which revealed subtle local changes; medium-range potentials are derived by incorporating contacts between HP1 and nucleosomes modified by H3K9me3, to incorporate experimental results of enhanced contacts for short chromatin fibers (12 nucleosomes); for long-range interactions we identify H3K9me3- and H3K27me3-associated contacts based on Hi-C maps with a machine learning approach. These combined multiscale effects can model methylation as a first approximation in our mesoscale chromatin model, and applications to gene systems offer new insights into the epigenetic regulation of genomes mediated by H3K9me3 and H3K27me3.
期刊介绍:
The Journal of Chemical Physics publishes quantitative and rigorous science of long-lasting value in methods and applications of chemical physics. The Journal also publishes brief Communications of significant new findings, Perspectives on the latest advances in the field, and Special Topic issues. The Journal focuses on innovative research in experimental and theoretical areas of chemical physics, including spectroscopy, dynamics, kinetics, statistical mechanics, and quantum mechanics. In addition, topical areas such as polymers, soft matter, materials, surfaces/interfaces, and systems of biological relevance are of increasing importance.
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