Regulation of Chromatin Modifications through Coordination of Nucleus Size and Epithelial Cell Morphology Heterogeneity.

Cell morphology heterogeneity within epithelial collectives is a pervasive phenomenon intertwined with tissue mechanical properties. Despite its widespread occurrence, the underlying mechanisms driving cell morphology heterogeneity and its consequential biological ramifications remain elusive. Here, we investigate the dynamic evolution of epithelial cell morphology and nucleus morphology during crowding, unveiling a consistent correlation between the two. Our investigation reveals a persistent log-normal probability distribution characterizing both cell and nucleus areas across diverse crowding stages and epithelial model systems. We showed that this morphological diversity arises from asymmetric partitioning during cell division and is perpetuated through actomyosin-mediated regulation of cell-nucleus size coordination. Moreover, we provide insights into the impact of nucleus morphology on chromatin dynamics, demonstrating that constraining nucleus area leads to downregulation of the euchromatic mark H3K9ac and upregulation of the heterochromatic mark H3K27me3 through modulation of histone demethylase UTX expression. These findings under-score the significance of cell morphology heterogeneity as a driver of chromatin state diversity, shaping functional variability within epithelial tissues.