Gene expression scaling with cell size: Insights across kingdoms

Gene expression is typically studied on a gene-by-gene basis, with regulation analyzed primarily in response to environmental or developmental cues. In contrast, much less is known about how intrinsic factors, such as cell size or DNA content, influence global gene expression patterns. Cell size varies significantly across different cell types and dynamically changes during the cell cycle. To maintain proper intracellular concentrations of biomolecules such as mRNAs and proteins, gene expression must be coordinated with cell size. Emerging evidence from diverse organisms, including bacteria, yeast, animals, and plants, demonstrates that transcriptional output scales with cell size, suggesting a conserved principle of gene regulation. However, the mechanisms by which cells sense their size and modulate gene expression accordingly remain poorly understood. In this review, we summarize recent advances in uncovering the molecular and cellular principles of gene expression scaling with cell size across kingdoms. We also highlight key open questions in the field, with a particular emphasis on how plant systems, still underexplored in this context, can provide additional insights into the fundamental principles of size-dependent gene regulation.