Defining and detecting links in chromosomes

Niewieczerzał, Szymon; Niemyska, Wanda; Sułkowska, Joanna I.

doi:10.1038/s41598-019-47999-4

Cited by 7 publications

(7 citation statements)

References 42 publications

(40 reference statements)

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“…Previous methods of population Hi-C could only give information about the average path of chromatin fibers constituting a given chromosome in millions of cells of a given type ( 6 , 22 , 23 ), and because chromosomes are highly dynamic ( 24 ), one could not use the population HI-C data to search for chromatin knots in individual chromosomes. Very recent studies using numerical simulations to analyze single-cell Hi-C data suggested that chromatin fibers in individual chromosomes can be knotted ( 25 , 26 , 27 , 28 ). However, the concluded knotting level was low with just one trefoil knot that appeared consistently in independent numerical simulations starting from the same single-cell Hi-C data of human chromosome 14 ( 28 ).…”

Section: Introductionmentioning

confidence: 99%

Chromatin Is Frequently Unknotted at the Megabase Scale

Goundaroulis

Aiden

Stasiak

2020

Biophysical Journal

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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.

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Section: Introductionmentioning

confidence: 99%

Chromatin Is Frequently Unknotted at the Megabase Scale

Goundaroulis

Aiden

Stasiak

2020

Biophysical Journal

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“…Therefore, if there were chromatin knots with cores smaller than 150 kb, they would not produce knotted parts of polygonal tracings and thus would be missed. However, this compares favourably, though, with single cell Hi-C modelling approach, which due to its 100 kb resolution (24)(25)(26)(27), can't detect chromatin knots if they would be even as large as 500 kb. On the other end of the scale, if the knot core would be larger than 2 Mb (size of analysed fragments), we would also miss it in our analysis.…”

Section: Discussionmentioning

confidence: 95%

“…Previous methods of population Hi-C could only give an information about the average path of chromatin fibres constituting a given chromosome in millions of cells of a given type (5,21,22) and since chromosomes are highly dynamic (23) one could not use the population HI-C data to search for chromatin knots in individual chromosomes. Very recent studies using numerical simulations to analyse single cell Hi-C data suggested that chromatin fibres in individual chromosomes can be knotted (24)(25)(26)(27). However, the concluded knotting level was low with just one trefoil knot that appeared consistently in independent numerical simulations starting from the same single cell Hi-C data of human chromosome 14 (27).…”

Section: Introductionmentioning

confidence: 99%

Chromatin is frequently unknotted at the megabase scale

Goundaroulis

Aiden

Stasiak

2019

Preprint

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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 highlyknotted 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.

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“…It can be helpful in search for knots, links and highly entangled configurations not previously described as well. Furthermore since this approach is much faster than other linking invariants it will provide a very useful technique to study loops in a single chromosome as well as chromosome entanglement in the cell 40,41 . Current methods allow one to describe single chromosomes with high resolution (thousands of beads).…”

Section: Discussionmentioning

confidence: 99%

GLN: a method to reveal unique properties of lasso type topology in proteins

Niemyska

Millett

Sułkowska

2020

Sci Rep

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Geometry and topology are the main factors that determine the functional properties of proteins. In this work, we show how to use the Gauss linking integral (GLN) in the form of a matrix diagram—for a pair of a loop and a tail—to study both the geometry and topology of proteins with closed loops e.g. lassos. We show that the GLN method is a significantly faster technique to detect entanglement in lasso proteins in comparison with other methods. Based on the GLN technique, we conduct comprehensive analysis of all proteins deposited in the PDB and compare it to the statistical properties of the polymers. We show how high and low GLN values correlate with the internal exibility of proteins, and how the GLN in the form of a matrix diagram can be used to study folding and unfolding routes. Finally, we discuss how the GLN method can be applied to study entanglement between two structures none of which are closed loops. Since this approach is much faster than other linking invariants, the next step will be evaluation of lassos in much longer molecules such as RNA or loops in a single chromosome.

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Defining and detecting links in chromosomes

Cited by 7 publications

References 42 publications

Chromatin Is Frequently Unknotted at the Megabase Scale

Chromatin Is Frequently Unknotted at the Megabase Scale

Chromatin is frequently unknotted at the megabase scale

GLN: a method to reveal unique properties of lasso type topology in proteins

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