Model of Euchromatin Clustering Resulting from Local Nucleosome Interactions

Euchromatin comprises accessible regions of the genome with relatively high transcriptional activity. DNA organization in euchromatin dictates gene expression and governs cell identity. In 1976, Finch and Klug characterized the structure of euchromatin as a regular 30-nm fiber based on in-vitro studies. This representation maintained widespread acceptance for decades. However, recent in-vivo imaging of euchromatin depicts a more heterogeneous architecture, with nucleosomes organizing into sporadic clusters. We develop a physical model that explains the heterogeneous architecture of euchromatin in vivo. According to our model, nucleosomes are patterned with a repressive epigenetic mark that is preferentially bound by a reader protein. Nearby reader proteins interact favorably and oligomerize, resulting in local compaction of the chromatin fiber. Heterogeneity in epigenetic-mark patterning and cooperative reader-protein binding cause variability in nucleosome density, with nucleosomes forming clusters that tend to align with marked domains. Using our model, we evaluate how conditions in the nucleoplasm affect euchromatin architecture, and we recapitulate nucleosome cluster-size distributions observed in recent experiments. Overall, this study offers an experimentally validated mechanism for euchromatin organization that explains the heterogeneous architecture observed in vivo responsible for controlling protein expression and cell identity.