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Entropic Competition between Supercoiled and Torsionally Relaxed Fibers Drives Chromatin Loop Extrusion

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Entropic Competition between Supercoiled and Torsionally Relaxed Fibers Drives Chromatin Loop Extrusion

Renáta Rusková 1,2 Dušan Račko 1

1Polymer Institute of the Slovak Academy of Sciences, Bratislava, Slovakia
2Faculty of Chemical and Food Industry STU, Bratislava, Slovakia

In 1977 Paulson and Laemmli dissolved meiotic chromosome – the X shaped one – and discovered that it consisted of about 100 kilobase DNA loops attached to a protein scaffold. Immediately it came to the question, if these loops have a biological function. If such a biological function should exist, the loops would need to exist also in interphase chromosomes, i.e. during the longest period of the cell cycle when the chromosomes exist in form of globules and perform their basic biological functions. Experimental discovery of the loops in the interphase chromosomes was challenging and became only possible after developing a group of experimental methods for chromosome conformation capture – also named 3C. After improvement of the method’s resolution in the new generation called Hi-C, the loops were independently discovered by three teams of authors in 2012.

Next question that naturally occurred was how these loops are created. In our paper, we propose a novel Brownian ratchet mechanism. Our model consists of fibre whose portion is stressed by axial rotations and a torsionally relaxed part. These two parts are separated by position of the SMC sliplink. The axial rotations mimic action of RNA-polymerase that performs transcription. The SMC is thermodynamically coupled with the fibre by exerting friction to axial rotations, thus preventing the supercoiling to escape. The supercoiled fibre can relieve from the increased energy only when the SMC moves further ahead from the transcription site and new portions of relaxed fibre flow into the emerging loop. The decrease in energy is temporary and soon replenished by the ongoing transcription and the SMC has to move again. 

This research was funded by the Grant Agency of the Ministry of Education, Science, Research and Sport of the Slovak Republic, Grant VEGA 2/0102/20 and COST 17 139.
Rusková, R.; and Račko, D.; „Entropic Competition between Supercoiled and Torsionally Relaxed Chromatin Fibers Drives Loop Extrusion through Pseudo-Topologically Bound Cohesin“ Biology, 2021, 10(2), 130.
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Biological significance 22.05.2021 16:07
Congratulations on the work - the contribution is based on the published results which already went through a peer-review process.
Just a comment, the abstract and presentation content is not composed ...
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Re: Biological significance 24.05.2021 20:27
Thank you for your comments and question. Cohesin and condensin are structural maintenance of chromosomes (SMC) proteins capable of chromatin loop extrusion, which is essential for chromosome packaging or u...Zobraziť celý komentár
Re: Re: Biological significance 24.05.2021 21:57
Thank you for your prompt response and I wish you plenty of new ideas in your work.
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