小柯机器人

美国约翰霍普金斯大学Taekjip Ha小组在基因组规模上测量了DNA力学。这一研究成果于2020年12月16日在线发表在国际学术期刊《自然》上。

研究人员开发了“ loop-seq”（一种高通量的测定方法，可测量DNA环化倾向），并确定跨越酿酒酵母V染色体、其他基因组区域和随机序列的270,806个50个碱基对长度DNA片段的内在环化能力。研究人员在转录起始位点（TSS）上游的核小体耗尽区域内发现了异常低的可弯曲性序列编码区域。接头DNA的低弯曲性通过染色质重塑因子INO80抑制了核小体滑入接头中，这解释了INO80如何在没有其他因素的情况下定义核小体耗尽的区域。全染色体的核小体特征是在二分体附近具有高DNA弯曲能力，而在接头附近具有低弯曲能力。

对于更深的基因体核小体，这种对比会增加，但是在同义密码子的随机替换后消失，这表明密码子选择的进化已受到基因体核小体周围DNA力学的影响。此外，研究人员表明，局部DNA力学影响通过TSS近端核小体的转录。总的来说，这一DNA力学的基因组规模图谱揭示了具有广泛功能含义的“力学代码”。

据悉，DNA的机械变形（例如弯曲）无处不在，并涉及多种细胞功能。但是，缺乏测量DNA力学性能的高通量工具，这限制了人们对DNA力学如何影响整个基因组中染色质活动的理解。

附：英文原文

Title: Measuring DNA mechanics on the genome scale

Author: Aakash Basu, Dmitriy G. Bobrovnikov, Zan Qureshi, Tunc Kayikcioglu, Thuy T. M. Ngo, Anand Ranjan, Sebastian Eustermann, Basilio Cieza, Michael T. Morgan, Miroslav Hejna, H. Tomas Rube, Karl-Peter Hopfner, Cynthia Wolberger, Jun S. Song, Taekjip Ha

Issue&Volume: 2020-12-16

Abstract: Mechanical deformations of DNA such as bending are ubiquitous and have been implicated in diverse cellular functions1. However, the lack of high-throughput tools to measure the mechanical properties of DNA has limited our understanding of how DNA mechanics influence chromatin transactions across the genome. Here we develop ‘loop-seq’—a high-throughput assay to measure the propensity for DNA looping—and determine the intrinsic cyclizabilities of 270,806 50-base-pair DNA fragments that span Saccharomyces cerevisiae chromosome V, other genomic regions, and random sequences. We found sequence-encoded regions of unusually low bendability within nucleosome-depleted regions upstream of transcription start sites (TSSs). Low bendability of linker DNA inhibits nucleosome sliding into the linker by the chromatin remodeller INO80, which explains how INO80 can define nucleosome-depleted regions in the absence of other factors2. Chromosome-wide, nucleosomes were characterized by high DNA bendability near dyads and low bendability near linkers. This contrast increases for deeper gene-body nucleosomes but disappears after random substitution of synonymous codons, which suggests that the evolution of codon choice has been influenced by DNA mechanics around gene-body nucleosomes. Furthermore, we show that local DNA mechanics affect transcription through TSS-proximal nucleosomes. Overall, this genome-scale map of DNA mechanics indicates a ‘mechanical code’ with broad functional implications.

DOI: 10.1038/s41586-020-03052-3

Source: https://www.nature.com/articles/s41586-020-03052-3

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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