Temperature-induced variation in gene expression burst size in metazoan cells

Ophélie Arnaud, Sam Meyer, Elodie Vallin, Guillaume Beslon, Olivier Gandrillon

Gene expression is an inherently stochastic process, owing to its dynamic molecular nature. Protein amount distributions, which can be acquired by cytometry using a reporter gene, can inform about the mechanisms of the underlying microscopic molecular system. By using different clones of chicken erythroid progenitor cells harboring different integration sites of a CMV-driven mCherry protein, we investigated the dynamical behavior of such distributions. We show that, on short term, clone distributions can be quickly regenerated from small population samples with a high accuracy. On longer term, on the contrary, we show variations manifested by correlated fluctuation in the Mean Fluorescence Intensity. In search for a possible cause of this correlation, we demonstrate that in response to small temperature variations cells are able to adjust their gene expression rate: a modest (2 °C) increase in external temperature induces a significant down regulation of mean expression values, with a reverse effect observed when the temperature is decreased. Using a two-state model of gene expression we further demonstrate that temperature acts by modifying the size of transcription bursts, while the burst frequency of the investigated promoter is less systematically affected. For the first time, we report that transcription burst size is a key parameter for gene expression that metazoan cells from homeotherm animals can modify in response to an external thermal stimulus.