Noise reduction as an emergent property of single-cell aging.

ABSTRACT

Noise-induced heterogeneity in gene expression is an inherent reality for cells. However, it is not well understood how noise strength changes for a single gene while the host cell is aging. Using a state-of-the-art microfluidic platform, we measure noise dynamics in aging yeast cells by tracking the generation-specific activity of the canonical GAL1 promoter. We observe noise reduction during normal aging of a cell, followed by a short catastrophe phase in which noise increased. We hypothesize that aging-associated increases in chromatin state transitions are behind the observed noise reduction and a stochastic model provides quantitative support to the proposed mechanism. Noise trends measured from strains with altered GAL1 promoter dynamics (constitutively active, synthetic with nucleosome-disfavoring sequences, and in the absence of RPD3, a global remodeling regulator) lend further support to our hypothesis. Observing similar noise dynamics from a different promoter (HHF2) provides support to the generality of our findings.Gene expression is a noisy process, but it is not known how noise in gene expression changes during the aging of single cells. Here the authors show that noise decreases during normal aging, and provide support for aging-associated increases in chromatin state transitions governing noise reduction.