遺伝子制御:ヌクレオソームのジャングルにおける修飾(Gene regulation: modification in the nucleosome jungle)

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2024-04-25 ミュンヘン大学(LMU)

LMUジーンセンターのヨハネス・スティグラー教授とドレスデン工科大学のフェリックス・ミュラー=プラニッツとの共同研究チームは、細胞核内の密集したクロマチンを通じて効果的に核小体を再配置する能力を持つ、ISWIと呼ばれる小さなクロマチン修飾酵素の研究を行いました。この酵素は、ATPを消費して核内を移動し、クロマチンが硬直するのを防ぎます。このプロセスの解明は、疾患への寄与や新たな治療法の開発への洞察を与える可能性があります。

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ヌクレオソーム配列におけるヌクレオソームのスライディングを触媒するISWI(ISWI catalyzes nucleosome sliding in condensed nucleosome arrays)

Petra Vizjak,Dieter Kamp,Nicola Hepp,Alessandro Scacchetti,Mariano Gonzalez Pisfil,Joseph Bartho,Mario Halic,Peter B. Becker,Michaela Smolle,Johannes Stigler & Felix Mueller-Planitz
Nature Structural & Molecular Biology  Published:25 April 2024
DOI:https://doi.org/10.1038/s41594-024-01290-x

遺伝子制御:ヌクレオソームのジャングルにおける修飾(Gene regulation: modification in the nucleosome jungle)

Abstract

How chromatin enzymes work in condensed chromatin and how they maintain diffusional mobility inside remains unexplored. Here we investigated these challenges using the Drosophila ISWI remodeling ATPase, which slides nucleosomes along DNA. Folding of chromatin fibers did not affect sliding in vitro. Catalytic rates were also comparable in- and outside of chromatin condensates. ISWI cross-links and thereby stiffens condensates, except when ATP hydrolysis is possible. Active hydrolysis is also required for ISWI’s mobility in condensates. Energy from ATP hydrolysis therefore fuels ISWI’s diffusion through chromatin and prevents ISWI from cross-linking chromatin. Molecular dynamics simulations of a ‘monkey-bar’ model in which ISWI grabs onto neighboring nucleosomes, then withdraws from one before rebinding another in an ATP hydrolysis-dependent manner, qualitatively agree with our data. We speculate that monkey-bar mechanisms could be shared with other chromatin factors and that changes in chromatin dynamics caused by mutations in remodelers could contribute to pathologies.

細胞遺伝子工学
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