

Hi-C experiments provide information about contacts, but an extruded loop cannot be told apart from any other occasional contact. Detecting extruded loops from microscopy is difficult due to their transient nature (≈10 min life-time ) and high volume-fraction of chromatin.

Most recently it was proposed that such loops are formed by an active (energy-dependent) process of loop extrusion, where loop-extruding motors associate to chromosomes, extrude loops, and dissociate, thus maintaining the chromosome polymer in the steady state with random loops (see for review). when they are not compacted for cell division, have long been conjectured to be folded into loops. Thus, our new framework allows interpretation of experimental data and suggests that interphase chromosomes are crumpled polymers further folded into a sequence of randomly positioned loops.Ĭhromosomes of high eukaryotes during interphase, i.e. We further show that excluded volume in real chains can induce osmotic and topological repulsion between loops. This agreement suggests that chromosomes are indeed organized into a sequence of randomly positioned loops and allows to estimate loop sizes. Remarkably, our model faithfully reproduces complex shapes of experimental contact probability curves universal among mammalian cells. Here, we introduce a model of a polymer with random loops, solve it analytically and extend it by simulations for real chains.
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It thus remains unknown how to obtain accurate and quantitative information about the nature of chromosomal looping from Hi-C. The lack of a tractable physical model of a polymer folded into loops limits our ability to interpret experimental data. The most comprehensive experimental information about chromosome spatial organization is provided by Hi-C experiments that measure the frequency of contacts between all chromosomal positions. While it was long suggested that mammalian chromosomes are folded into loops, experimental detection of such loops has remained a daunting task. Chromosomes are exceedingly long polymers compacted in a cell nucleus.
