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ISW1和CHD1染色质重塑因子抑制活酵母细胞中的整体核小体动力学。

The ISW1 and CHD1 chromatin remodelers suppress global nucleosome dynamics in living yeast cells.

作者信息

Xu Zhuwei, Prajapati Hemant K, Eriksson Peter R, Clark David J

机构信息

Division of Developmental Biology, Eunice Kennedy-Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.

出版信息

Sci Adv. 2025 Aug;11(31):eadw7108. doi: 10.1126/sciadv.adw7108. Epub 2025 Aug 1.

Abstract

The budding yeast genome is globally accessible to DNA methyltransferases in living cells, unlike in isolated nuclei, where it is mostly inaccessible. Here, we assess the roles of the RSC, ISW1, and CHD1 adenosine 5'-triphosphate-dependent chromatin remodelers in generating nucleosome dynamics in vivo. We compare DNA methylation rates in wild-type cells and chromatin remodeler mutants by normalizing nuclear methylation rates to the nonnucleosomal mitochondrial DNA methylation rate in each strain. Depletion of both Isw1 and Chd1 increases the normalized methylation rate, suggesting that these remodelers act together to suppress nucleosome dynamics. Separate depletion of Isw1, Chd1, or Rsc8 has little effect. A decaying sine wave model used to fit nucleosome phasing data shows that nucleosome dynamics decrease with distance from the promoter in an Isw1/Chd1-dependent manner. Furthermore, the TFIIIB and TFIIIC transcription factors exhibit differential dynamics at transfer RNA genes in vivo. Our analysis provides insight into nucleosome and transcription factor dynamics in vivo.

摘要

与分离的细胞核不同,在分离的细胞核中芽殖酵母基因组大多无法被DNA甲基转移酶接近,而在活细胞中芽殖酵母基因组在整体上可被DNA甲基转移酶接近。在这里,我们评估了RSC、ISW1和CHD1三磷酸腺苷依赖性染色质重塑因子在体内产生核小体动力学过程中的作用。我们通过将每个菌株的核甲基化率标准化为非核小体线粒体DNA甲基化率,比较了野生型细胞和染色质重塑因子突变体中的DNA甲基化率。Isw1和Chd1的缺失均会增加标准化甲基化率,这表明这些重塑因子共同作用以抑制核小体动力学。单独缺失Isw1、Chd1或Rsc8几乎没有影响。用于拟合核小体相位数据的衰减正弦波模型表明,核小体动力学以Isw1/Chd1依赖性方式随着与启动子距离的增加而降低。此外,TFIIIB和TFIIIC转录因子在体内的转运RNA基因处表现出不同的动力学。我们的分析为体内核小体和转录因子动力学提供了见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f0a/12315965/9b5185ce0c9a/sciadv.adw7108-f1.jpg

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