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基因组尺度下DNA力学性质的预测揭示了DNA柔韧性潜在的新功能作用。

Predictions of DNA mechanical properties at a genomic scale reveal potentially new functional roles of DNA flexibility.

作者信息

Back Georg, Walther Dirk

机构信息

Max Planck Institute of Molecular Plant Physiology, Am Mühlenberg 1, Potsdam-Golm 14476, Germany.

出版信息

NAR Genom Bioinform. 2023 Nov 6;5(4):lqad097. doi: 10.1093/nargab/lqad097. eCollection 2023 Dec.

DOI:10.1093/nargab/lqad097
PMID:37954573
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10632188/
Abstract

Mechanical properties of DNA have been implied to influence many of its biological functions. Recently, a new high-throughput method, called loop-seq, which allows measuring the intrinsic bendability of DNA fragments, has been developed. Using loop-seq data, we created a deep learning model to explore the biological significance of local DNA flexibility in a range of different species from different kingdoms. Consistently, we observed a characteristic and largely dinucleotide-composition-driven change of local flexibility near transcription start sites. In the presence of a TATA-box, a pronounced peak of high flexibility can be observed. Furthermore, depending on the transcription factor investigated, flanking-sequence-dependent DNA flexibility was identified as a potential factor influencing DNA binding. Compared to randomized genomic sequences, depending on species and taxa, actual genomic sequences were observed both with increased and lowered flexibility. Furthermore, in , mutation rates, both and fixed, were found to be associated with relatively rigid sequence regions. Our study presents a range of significant correlations between characteristic DNA mechanical properties and genomic features, the significance of which with regard to detailed molecular relevance awaits further theoretical and experimental exploration.

摘要

DNA的机械特性被认为会影响其许多生物学功能。最近,一种名为loop-seq的新的高通量方法被开发出来,它可以测量DNA片段的内在弯曲性。利用loop-seq数据,我们创建了一个深度学习模型,以探索不同界的一系列不同物种中局部DNA柔韧性的生物学意义。我们一致观察到转录起始位点附近局部柔韧性存在特征性且在很大程度上由二核苷酸组成驱动的变化。在存在TATA框的情况下,可以观察到明显的高柔韧性峰值。此外,根据所研究的转录因子,侧翼序列依赖性DNA柔韧性被确定为影响DNA结合的一个潜在因素。与随机基因组序列相比,根据物种和分类群的不同,实际基因组序列的柔韧性既有增加的情况,也有降低的情况。此外,在……中,发现突变率(包括……和固定突变率)与相对刚性的序列区域相关。我们的研究展示了特征性DNA机械特性与基因组特征之间的一系列显著相关性,其在详细分子相关性方面的意义有待进一步的理论和实验探索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7b/10632188/ecc54ea135d6/lqad097fig10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7b/10632188/6b5c49fdc909/lqad097fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7b/10632188/8b76262d2a75/lqad097fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7b/10632188/38fb5d9a3d69/lqad097fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7b/10632188/5ea30f8c2602/lqad097fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7b/10632188/01395d57359c/lqad097fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7b/10632188/9551c15d6f6d/lqad097fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7b/10632188/cbd3cf3bba64/lqad097fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7b/10632188/deeea3e19786/lqad097fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7b/10632188/355a01445cf5/lqad097fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7b/10632188/ecc54ea135d6/lqad097fig10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7b/10632188/6b5c49fdc909/lqad097fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7b/10632188/8b76262d2a75/lqad097fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7b/10632188/38fb5d9a3d69/lqad097fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7b/10632188/5ea30f8c2602/lqad097fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7b/10632188/01395d57359c/lqad097fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7b/10632188/9551c15d6f6d/lqad097fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7b/10632188/cbd3cf3bba64/lqad097fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7b/10632188/deeea3e19786/lqad097fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7b/10632188/355a01445cf5/lqad097fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc7b/10632188/ecc54ea135d6/lqad097fig10.jpg

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