RT Journal Article
SR Electronic
T1 Chromatin is frequently unknotted at the megabase scale
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 762872
DO 10.1101/762872
A1 Goundaroulis, Dimos
A1 Aiden, Erez Lieberman
A1 Stasiak, Andrzej
YR 2019
UL http://biorxiv.org/content/early/2019/09/09/762872.abstract
AB 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 3d 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 whether a genomic trajectory is knotted in the setting of experimental noise. We analyse 4727 deposited genomic trajectories of a 2Mb long chromatin interval from 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 is consistent with a model where, at the scales probed, the human genome is often free of knots.