Nucleosome spacing controls chromatin spatial structure and accessibility.

ABSTRACT

Recent research highlights the significance of the three-dimensional structure of chromatin in regulating various cellular processes, particularly transcription. This is achieved through dynamic chromatin structures that facilitate long-range contacts and control spatial accessibility. Chromatin consists of DNA and a variety of proteins, of which histones play an essential structural role by forming nucleosomes. Extensive experimental and theoretical research in recent decades has yielded conflicting results about key factors that regulate the spatial structure of chromatin, which remains enigmatic. By using a computer model that allows us to simulate chromatin volumes containing physiological nucleosome concentrations, we investigated whether nucleosome spacing or nucleosome density is fundamental for three-dimensional chromatin accessibility. Unexpectedly, the regularity of the nucleosome spacing is crucial for determining the accessibility of the chromatin network to diffusive processes, whereas variation in nucleosome concentrations has only minor effects. Using only the basic physical properties of DNA and nucleosomes was sufficient to generate chromatin structures consistent with published electron microscopy data. Contrary to other work, we found that nucleosome density did not substantially alter the properties of chromatin fibers or contact probabilities of genomic loci. No breakup of fiber-like structures was observed at high molar density. These findings challenge previous assumptions and highlight the importance of nucleosome spacing as a key driver of chromatin organization. These results identified changes in nucleosome spacing as a tentative mechanism for altering the spatial chromatin structure and thus genomic functions.