Noise reduction as an emergent property of single-cell aging

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.