Modular effects of gene promoters and chromatin environments on noise in gene expression

Genetically identical cells growing in the same environment can have large differences in gene expression. Both locally acting cis -regulatory sequences (CRS) and the regional properties of chromosomal environments influence the noisiness of a gene’s expression. Whether or not local CRS and regional chromosomal environments act independently on noise, or whether they interact in complex ways is unknown. To address this question, we measured the expression mean and noise of reporter genes driven by different CRS at multiple chromosomal locations. While a strong power law relationship between mean expression and noise explains ~60% of noise for diverse promoters across chromosomal locations, modeling the residual mean-independent noise suggests that chromosomal environments have strong effects on expression noise by influencing how quickly genes transition from their inactive states to their active states and that the effects of local CRS and regional chromatin on noise are largely independent. Our results support a modular genome in which regional chromatin modifies the inherent relationship between the mean and noise of expression regardless of the identity of the promoter sequence.