# Regulation of chromatin modifications through coordination of nucleus size and epithelial cell morphology heterogeneity

## TL;DR

The paper shows how cell shape differences in epithelial tissues affect chromatin modifications, influencing gene regulation and tissue function.

## Contribution

The study reveals that asymmetric cell division and nucleus morphology drive chromatin state diversity through histone modification regulation.

## Key findings

- Cell and nucleus morphology heterogeneity follows a log-normal distribution across epithelial systems.
- Nucleus size regulates H3K27me3 levels via histone demethylase UTX.
- Nucleus morphology influences euchromatic and heterochromatic marks like H3K9ac and H3K27me3.

## Abstract

Cell morphology heterogeneity is pervasive in epithelial collectives, yet the underlying mechanisms driving such heterogeneity and its consequential biological ramifications remain elusive. Here, we observed a consistent correlation between the epithelial cell morphology and nucleus morphology during crowding, revealing a persistent log-normal probability distribution characterizing both cell and nucleus areas across diverse epithelial model systems. We showed that this morphological diversity arises from asymmetric partitioning during cell division. Next, we provide insights into the impact of nucleus morphology on chromatin modifications. We demonstrated that constraining nucleus leads to downregulation of the euchromatic mark H3K9ac and upregulation of the heterochromatic mark H3K27me3. Furthermore, we showed that nucleus size regulates H3K27me3 levels through histone demethylase UTX. These findings highlight the significance of cell morphology heterogeneity as a driver of chromatin state diversity, shaping functional variability within epithelial tissues.

Cell morphology heterogeneity in epithelial tissues, driven by asymmetric cell division, correlates with nucleus morphology and impacts chromatin state diversity through histone modifications.