Deletion of the transcription factors Hsf1, Msn2 and Msn4 in yeast uncovers transcriptional reprogramming in response to proteotoxic stress

Cells not only adapt to environmental changes, but they also “remember” specific signals, allowing them to respond more rapidly to future stressors. This phenomenon, known as transcriptional memory, is orchestrated by a complex interplay of epigenetics, transcription regulators and RNA metabolism factors. Although transcriptional memory has been well-studied in various contexts, its role in the heat shock (HS) response of yeast remains largely unexplored. In our study, we delve into the dynamics of HS memory in wild-type yeast and amip6Δ mutant, which lacks the RNA-binding protein Mip6. Notably, Mip6 has been shown to influence the expression of key stress-related genes and maintain low Msn2/4-dependent transcript levels under standard conditions. Our transcriptomic analysis offers novel insights into how yeast cells remember HS exposure. We uncover striking differences in gene expression patterns depending on whether genes are induced or repressed during HS memory. Furthermore, we find that an initial 15-minute heat shock triggers a response that becomes attenuated with just 5 additional minutes of stress. While the response kinetics between memory and non-memory conditions are similar, we report a subtle but important role for Mip6 in fine-tuning transcriptional memory and adaptation to heat stress. Biochemical and genetic evidence also suggests that Mip6 cooperates with alternative survival pathways independent of MSN2/4, and functionally interacts with the Rpd3 histone deacetylase complex, a key player in transcriptional memory and the HS response. These findings open up new avenues for understanding the molecular mechanisms behind heat stress adaptation in eukaryotes.

show abstract

Full Circle: When HSFs bring the heat—mapping the transcriptional circuitries of HSF-type regulators in Candida albicans

Znaidi

2024

mSphere

View full text Add to dashboard Cite

Heat shock factor (HSF)-type regulators are stress-responsive transcription factors widely distributed among eukaryotes, including fungi. They carry a four-stranded winged helix-turn-helix DNA-binding domain considered as the signature domain for HSFs. The genome of the opportunistic yeast Candida albicans encodes four HSF members, namely, Sfl1, Sfl2, Skn7, and the essential regulator, Hsf1. C. albicans HSFs do not only respond to heat shock and/or temperature variation but also to CO 2 levels, oxidative stress, and quorum sensing, acting this way as central decision makers. In this minireview, I follow on the heels of my mSphere of Influence commentary (2020) to provide an overview of the repertoire of HSF regulators in Saccharomyces cerevisiae and C. albicans and describe how their genetic perturbation in C. albicans , coupled with genome-wide expression and location analyses, allow to map their transcriptional circuitry. I highlight how they can regulate, in common, a crucial developmental program: filamentous growth.

show abstract

Deletion of the transcription factors Hsf1, Msn2 and Msn4 in yeast uncovers transcriptional reprogramming in response to proteotoxic stress

Cited by 4 publications

References 96 publications

Surviving the heat: the role of macromolecular assemblies in promoting cellular shutdown

Surviving the heat: the role of macromolecular assemblies in promoting cellular shutdown

Decoding Transcriptional Memory in Yeast Heat Shock and the Functional Implication of the RNA Binding Protein Mip6

Full Circle: When HSFs bring the heat—mapping the transcriptional circuitries of HSF-type regulators in Candida albicans

Contact Info

Product

Resources

About