Presentation Information

[SS17-02]Principle of nucleosome condensation: a unified framework of chromatin domain formation

Shin Fujishiro1, *Masaki Sasai1,2 (1. Kyoto University (Japan), 2. Nagoya University (Japan))

Keywords:

chromatin domains,nucleosome condensation,cohesin,genomes

In many organisms, chromatin is organized into domains of sub-megabase (sub-Mb) in size. These domains, identified through Hi-C methods, are known as topologically associating domains (TADs). Understanding how these domains are formed is crucial, as they function as regulatory units of the genome. It is particularly important to explore the significant variation in domain sizes across different organisms. For example, typical domain sizes are about 10 kilobases (kb) in yeast, several hundred kb in mammals, and several Mb in axolotl. While the loop-extrusion mechanism has been proposed as an explanation for domain formation in mammalian genomes, a comprehensive theory that applies to various organisms is lacking. In this talk, we will introduce a mechanism that may provide a consistent explanation for domain formation across species.

In vitro experiments have shown that attractions among nucleosomes can cause chromatin to condense into liquid droplets. We suggest that these attractions may also lead to condensation within cells, resulting in chromatin domain formation (Fujishiro et al. 2025 Curr Opin Str Biol). We term these tendencies found both in vitro and in various cells as "the principle of nucleosome condensation." Regions of chromatin characterized by histone acetylation or nucleosome depletion should exhibit reduced interactions among nucleosomes, causing these open chromatin regions to be excluded from the condensed core of the domain. Additionally, large transcription factors can disrupt attractions among nucleosomes, causing regions associated with these factors to shift to the domain surface, acting like "buoys" (Maeshima et al. 2015 J Phys Cond Matt). Based on the principle of nucleosome condensation, we propose that thermodynamically stable domains have a critical size determined by the balance of core condensation and surface energy, which is determined by the ratio of open chromatin within the domain. As a result, genomes with fewer (more) open chromatin regions are likely to have larger (smaller) domains. This explanation leads to a unified framework for understanding the distribution of domain sizes, accounting for variability across organisms. Using the principle of nucleosome condensation, we also highlight the roles of cohesin and boundary elements, such as CTCF, in stabilizing domain boundaries. We present a dynamic model that involves an ensemble of cohesin molecules, which helps to explain the features observed in Hi-C data.