The organization and dynamics of chromatin are essential for understanding gene regulation and cell function. In order to simulate these processes accurately, researchers use coarse-grained bead-spring polymer models to describe chromatin. However, the dimensions of the beads, their elastic properties, and the nature of the inter-bead potentials have been largely unknown.

To address this, we utilized publicly available nucleosome-resolution contact probability (Micro-C) data to systematically coarse-grain chromatin and predict important quantities for polymer representation of chromatin. We computed size distributions of chromatin beads for different coarse-graining scales, quantified fluctuations and distributions of bond lengths between neighboring regions, and derived effective spring constant values.

Our findings suggest that contrary to prevalent notions, coarse-grained chromatin beads should be considered soft particles that can overlap. We derived an effective inter-bead soft potential and quantified an overlap parameter, which provides crucial insights into the nature of chromatin packing. We also computed angle distributions between neighboring bonds, which gave insights into intrinsic folding and local bendability of chromatin.

Interestingly, we found that the bead sizes, bond lengths, and bond angles showed different mean behavior at the boundaries of chromatin domains. We integrated our findings into a coarse-grained polymer model and provided quantitative estimates of all model parameters, which can serve as a foundational basis for all future coarse-grained chromatin simulations.

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Chromatin topology plays a crucial role in gene expression and development. Disruption of long-range chromatin contacts due to mutations in the PH protein can lead to developmental defects. Our work aimed to understand the molecular mechanism underlying this phenomenon, which could potentially provide a better understanding of the genetic basis of developmental defects and diseases. This work was in collaboration with Prof. Ajazul H Wani's group at the University of Kashmir, India.

Prof. Ajazul Wani's group performed the experimental work investigating the effect of the SAM domain mutation on nucleosome occupancy and accessibility on a genome-wide scale. Our modeling work complemented the experimental work by providing insights into the interplay between distant chromatin contacts and nucleosome occupancy. We performed polymer simulations to investigate how the disruption of PH polymerization affects the organization of chromatin and nucleosome occupancy.

Our polymer simulations revealed that nucleosome density increases when contacts between different regions of chromatin are established. Our results show that nucleosome density increases when contacts between different regions of chromatin are established, which suggests that higher-order organization can have a top-down causation effect on nucleosome occupancy.

In conclusion, our modeling work contributed to a better understanding of the molecular mechanism underlying the regulation of chromatin organization by studying the interplay between distant chromatin contacts and nucleosome occupancy, both of which are regulated by PH polymerization. This work could potentially provide a better understanding of the genetic basis of developmental defects and diseases.