Chromatin Is Frequently Unknotted at the Megabase Scale
Chromatin Is Frequently Unknotted at the Megabase Scale
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DOI：
10.1016/j.bpj.2019.11.002
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发表时间：
2020-05-05
影响因子：
3.4
通讯作者：
Stasiak, Andrzej
中科院分区：
文献类型：
--
作者：
Goundaroulis, Dimos;Aiden, Erez Lieberman;Stasiak, Andrzej
人类基因组中的结将极大地影响从转录到基因调控的各种细胞过程。迄今为止，还不可能直接检查体内基因组中结的存在。最近，连续荧光原位杂交的方法已经使得有可能在体内测量几十个连续基因组位点的三维位置。然而，确定基因组轨迹是否打结仍然具有挑战性，因为单个基因座定位中的小误差可以将未打结的轨迹转化为高度打结的轨迹，反之亦然。在这里，我们使用随机闭合分析来确定基因组轨迹在实验噪音的背景下是否打结。我们分析了4727个沉积的基因组轨迹的2 Mb长的染色质间隔从人类21号染色体。对于这些轨迹中的243个，尽管存在定位误差的可能性，但可以可靠地确定它们的打结。引人注目的是，在这243个病例中，每个病例的轨迹都是解开的。我们注意到一个潜在的偏倚来源，因为打结轮廓可能更难以可靠地解决。然而，我们的数据与一个模型是一致的，在这个模型中，在所探测的尺度上，人类基因组通常没有结。
Knots in the human genome would greatly impact diverse cellular processes ranging from transcription to gene regulation. To date, it has not been possible to directly examine the genome in vivo for the presence of knots. Recently, methods for serial fluorescent in situ hybridization have made it possible to measure the three-dimensional position of dozens of consecutive genomic loci in vivo. However, the determination of whether genomic trajectories are knotted remains challenging because small errors in the localization of a single locus can transform an unknotted trajectory into a highly knotted trajectory and vice versa. Here, we use stochastic closure analysis to determine if a genomic trajectory is knotted in the setting of experimental noise. We analyze 4727 deposited genomic trajectories of a 2-Mb-long chromatin interval from human chromosome 21. For 243 of these trajectories, their knottedness could be reliably determined despite the possibility of localization errors. Strikingly, in each of these 243 cases, the trajectory was unknotted. We note a potential source of bias insofar as knotted contours may be more difficult to reliably resolve. Nevertheless, our data are consistent with a model in which, at the scales probed, the human genome is often free of knots.