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

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.