Zinc starvation induces a stress response inSaccharomyces cerevisiae that is mediated by the Msn2p and Msn4p transcriptional activators

Abstract

During the production of wine and beer, the yeast Saccharomyces cerevisiae can encounter an environment that is deficient in zinc, resulting in a 'sluggish' or a 'stuck' ferment. It has been shown that the Zap1p-transcription factor induces the expression of a regulon in response to zinc deficiency; however, it was evident that a separate regulon was also activated during zinc deficiency in a Zap1p-independent manner. This study discovered the Msn2p and Msn4p (Msn2/4p) transcriptional activator proteins to be an additional control mechanism inducing the stress response during zinc deficiency. Promoter sequence analysis identified the stress-response element (STRE) motif, recognized by Msn2/4p, and was significantly enriched in the promoters of genes induced by zinc deficiency. An investigation using genome-wide analyses revealed a distinct regulon consisting of STRE-containing genes whose zinc-responsive expression was abolished in an msn2 msn4 double mutant. An STRE-driven lacZ reporter construct confirmed that expression of the genes within this regulon was perturbed by the deletion of MSN2 and MSN4 and also implicated Hog1p as a contributing factor. This research provides a better understanding of the molecular mechanisms involved in the yeast response to zinc deficiency during fermentation.

Activation of the Yeast UBI4 Polyubiquitin Gene by Zap1 Transcription Factor via an Intragenic Promoter Is Critical for Zinc-deficient Growth

“…A previous report suggested that stress response genes may be activated by zinc deficiency via the Msn2/4 transcription factors (31). To determine whether either Msn2/Msn4 or the heat shock factor Hsf1 play a role in regulating UBI4 in response to zinc supply, we generated an allele in which the Hsf1 binding site (HSE) was deleted from the UBI4 promoter (ubi4 HSEmut ).…”

Expression Profiling Reveals an Unexpected Growth-Stimulating Effect of Surplus Iron on the Yeast Saccharomyces cerevisiae

“…Furthermore, several stress-responsive genes were also upregulated in surplus iron at 4 h, such as HSP12, HOR7, LSP1, SOD2, GRX4, CCC1, GSY1, and HSP31. In particular, HSP12, HOR7, SOD2, CCC1 and HSP31 contain a stress response element (STRE) consensus sequence in their promoter regions, and all are target genes of the stress-resistant transcription factors Msn2/4 (Gauci et al, 2009;Martinez-Pastor et al, 1996). For instance, Hsp12 is a plasma membrane protein induced by stress conditions that probably initially perceives extracellular surplus iron.…”

“…The vacuolar iron transporter Ccc1 that is induced by Msn2/4 facilitates the storage of surplus intracellular iron in the vacuole to alleviate high-iron toxicity. In addition to Msn2/4-dependent stress-responsive genes, many upregulated genes in other metabolic pathways are also targets of Msn2/4 (Table 1) (Gauci et al, 2009). Therefore, we further checked changes in the transcription of MSN2/4, with the result that MSN4 increased 1.5-fold and 1.75-fold under 5 mM of Fe 3+ at 1 and 4 h, respectively, compared to the stable transcription of MSN2 in iron-surplus conditions.…”

Transcriptomic analysis of thermotolerant yeastKluyveromyces marxianusin multiple inhibitors tolerance

“…41 Table 2 lists DEGs which are reported to be controlled via the stress responsive element (STRE) in S. cerevisiae. 41,42 As shown in Table 2, quite a few stress-responsive genes were down-regulated under the stress of multiple inhibitors, such as HXK1, GPH, TDH1, TDH3, PGM, CTT1 etc., while there were also some genes up-regulated such as SSA3, SOD2, TDH2, HSP26, HSP31, ALD, MDH2 etc. Our RNA-seq results showed that there was only MSN2 in K. marxianus and with no signicant change under the multiple inhibitors condition (data not shown), indicating that this MSN2 might be different to that in S. cerevisiae.…”

“…K. marxianus YHJ010 was precultivated in 5 ml of YPD medium at 42 C overnight. Then the cells were transferred into 500 ml Erlenmeyer asks containing 100 ml of the YPD medium with or without mixed inhibitors containing 0.…”