Supplementary information : Negative feedback buffers effects of regulatory variants

Standfirst text and highlights: Local trans regulation, mainly due to negative feedback, buffers effects of cis-regulatory variants by about 15%. This buffering is stronger for essential genes and genes with low to middle expression levels, for which tight regulation matters most. • Novel experimental design using expression of a diploid hybrid and its haploid spores allows systematic dissection of cis and local trans regulation • Local trans effects buffer effects of cis-regulatory variants in yeast by typically 15% • Local trans buffering is primarily due to negative feedback • Negative feedback as robustness strategy for genes with low to medium expression level