Kumar, P. B. S. | Search bioRxiv

bioRxiv2024

Interplay between cohesin kinetics and polymer relaxation modulates chromatin-domain structure and dynamics

Even though the three-dimensional static organization of chromatin is highly studied, chromatin is a dynamic structure, and time-dependent changes are crucial for biological function. While it is known that both intra-chromatin interaction and loop extrusion are crucial to understanding chromatin organization, what is their respective role in deciding the nature of spatial and temporal organization is not clear. Simulating a model with active loop extrusion and intra-chromatin interactions, we show that under certain conditions, the measurable dynamic quantities are dominated by the loop extrusion, even though the population-averaged contact map (structure) can be dominated by intra-chromatin interactions, with loop extrusion playing no major role. Our results show that the dynamic scaling exponents with loop extrusion are consistent with the experimental observations and can be very different from those predicted by existing fractal-globule models for chromatin. We argue that one needs to measure both the structure and dynamics simultaneously to unambiguously interpret the organization of chromatin.

biophysics↗

bioRxiv2023

Nonequilibrium switching of segmental states can influence compaction of chromatin

Knowledge about the dynamic nature of chromatin organization is essential to understand the regulation of processes like DNA transcription and repair. While most models assume protein organization and chemical states along chromatin as static, experiments have shown that these are dynamic and lead to the switching of chromatin segments between different physical states. To understand the implications of this inherent nonequilibrium switching, we present a diblock copolymer model of chromatin, with switching of its segmental states between two states, mimicking active/repressed or protein unbound/bound states. We show that competition between switching timescale Tt, polymer relaxation timescale{tau} p, and segmental relaxation timescale{tau} s can lead to non-trivial changes in chromatin organization, leading to changes in local compaction and contact probabilities. As a function of the switching timescale, the radius of gyration of chromatin shows a non-monotonic behavior with a prominent minimum when Tt {approx}{tau} p and a maximum when Tt {approx}{tau} s. We find that polymers with a small segment length exhibit a more compact structure than those with larger segment lengths. We also find that the switching can lead to higher contact probability and better mixing of far-away segments. Our study also shows that the nature of the distribution of chromatin clusters varies widely as we change the switching rate. Significance statementDifferent cells in multicellular organisms have the same DNA but different functions. The function of any given cell type can be time-dependent. The current understanding is that differences in gene expression arising from local compaction and the probability for far-away regulatory segments to come in contact play an important role in establishing these differences. The necessary structural variations are achieved through a combination of changes in the chemical and physical states of chromatin regions. In this paper, we present a model for chromatin accounting for the dynamic switching of chromatin regions between different chemical and physical states. We demonstrate the implications of such switching in determining the local 3D structure of chromatin.

biophysics↗