Control of Gene Expression via the Yeast CWI Pathway

Abstract

Living cells exposed to stressful environmental situations can elicit cellular responses that guarantee maximal cell survival. Most of these responses are mediated by mitogen-activated protein kinase (MAPK) cascades, which are highly conserved from yeast to humans. Cell wall damage conditions in the yeast Saccharomyces cerevisiae elicit rescue mechanisms mainly associated with reprogramming specific transcriptional responses via the cell wall integrity (CWI) pathway. Regulation of gene expression by this pathway is coordinated by the MAPK Slt2/Mpk1, mainly via Rlm1 and, to a lesser extent, through SBF (Swi4/Swi6) transcription factors. In this review, we summarize the molecular mechanisms controlling gene expression upon cell wall stress and the role of chromatin structure in these processes. Some of these mechanisms are also discussed in the context of other stresses governed by different yeast MAPK pathways. Slt2 regulates both transcriptional initiation and elongation by interacting with chromatin at the promoter and coding regions of CWI-responsive genes but using different mechanisms for Rlm1- and SBF-dependent genes. Since MAPK pathways are very well conserved in eukaryotic cells and are essential for controlling cellular physiology, improving our knowledge regarding how they regulate gene expression could impact the future identification of novel targets for therapeutic intervention.

Systematic Identification of Essential Genes Required for Yeast Cell Wall Integrity: Involvement of the RSC Remodelling Complex

“…Upon cell wall stress conditions, Slt2 phosphorylates and activates the transcription factor Rlm1 to recruit both elements to the promoters of CWI-responsive genes in complex with SWI/SNF [ 9 ]. SWI/SNF activity is necessary to evict nucleosomes positioned in this region and permit pre-initiation complex (PIC) assembly in cooperation with the SAGA complex, which mediates histone acetylation for nucleosome reorganization [ 6 , 12 ]. The results described here suggest that the RSC complex could cooperate with SWI/SNF and SAGA complexes for the chromatin remodelling necessary for the transcriptional activation of CWI-dependent genes upon stress.…”

“…This response includes changes in the synthesis and crosslinking of different polymers, and increased expression levels of genes functionally related to cell wall maintenance [ 3 , 4 ]. Cell wall stress adaptive responses in yeast are mainly regulated by the cell wall integrity (CWI) MAPK pathway, which includes a conserved MAPK module [ 5 , 6 ]. This module is activated through a cascade of phosphorylation events, which ultimately lead to the phosphorylation of the MAPK of the pathway, Slt2/Mpk1.…”

Post-Translational Modifications of Histones Are Versatile Regulators of Fungal Development and Secondary Metabolism

“…Several pieces of evidence are compatible with this hypothesis, including a tight link between Acyl-CoA content and chromatin regulation (reviewed in [ 184 ]). This balancing situation can be viewed as a competition of metabolism with histone acylation [ 185 , 186 , 187 ]. As a whole, understanding the Histone Code related to secondary metabolism regulations may allow the development of optimized approaches to fight against fungal contaminations or to manage the development of new pharmaceutical drugs.…”

Contribution of Model Organisms to Investigating the Far-Reaching Consequences of PRPP Metabolism on Human Health and Well-Being

“…The general architecture of the MAPK (mitogen-activating protein kinase) pathway in eukaryotes is illustrated in Figure 4 a. Excellent reviews of the yeast CWI pathway and the extent of its influence on yeast physiology have been published [ 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 ]. Sc PRS mutant strains have consistently shown varying degrees of sensitivity to the purine analogue, caffeine (1,3,7-tri-methylxanthine), thus compromising CWI signalling via the MAPK (mitogen-activated protein kinase) [ 64 , 74 , 79 , 82 , 92 ].…”