Dynamic sumoylation is essential in yeast for suppressing stress-induced gene expression in non-stress conditions.

Environmental stresses such as heat shock trigger widespread changes in gene expression, collectively known as the environmental stress response (ESR), along with a global increase in SUMO conjugation. However, whether elevated sumoylation contributes to establishing the ESR gene expression program remains unclear. Here, we show that mutant yeast with constitutively high sumoylation levels due to a defect in the SUMO protease Ulp1, ulp1-mt, displays stress-like gene expression changes, including upregulation of heat shock-induced genes, in the absence of external stress. The ESR regulators Hog1 and Msn2 are constitutively active in this mutant and drive the observed transcriptional changes. Surprisingly, both heat shock and Ulp1 impairment lead to a reduction in levels of SUMO that are stably associated with gene loci, suggesting that increased sumoylation of tightly-bound chromatin factors does not underlie stress-like transcriptional changes. Intriguingly, mutant yeast with reduced sumoylation due to impairment of sumoylation enzymes also show ESR-like transcription effects, including expression of heat shock genes. These findings indicate that disruption of normal sumoylation/desumoylation cycling, rather than absolute SUMO conjugation levels, triggers an ESR-like transcriptional program. This work reveals a new layer of regulation in stress-responsive gene expression and implicates SUMO homeostasis as key in modulating transcriptional stress signaling.