Uncovering divergence in gene expression regulation in the adaptation of yeast to nitrogen scarcity

Carlos A. Villarroel, MacArena Bastías, Paulo Canessa, Francisco A. Cubillos

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)


Saccharomyces cerevisiae rewires its transcriptional output to survive stressful environments, such as nitrogen scarcity under fermentative conditions. Although divergence in nitrogen metabolism among natural yeast populations has been reported, the impact of regulatory genetic variants modulating gene expression and nitrogen consumption remains to be investigated. Here, we employed an F1 hybrid from two contrasting S. cerevisiae strains, providing a controlled genetic environment to map cis factors involved in the divergence of gene expression regulation in response to nitrogen scarcity. We used a dual approach to obtain genome-wide allele-specific profiles of chromatin accessibility, transcription factor binding, and gene expression through ATAC-seq (assay for transposase accessible chromatin) and RNA-seq (transcriptome sequencing). We observed large variability in allele-specific expression and accessibility between the two genetic backgrounds, with a third of these differences specific to a deficient nitrogen environment. Furthermore, we discovered events of allelic bias in gene expression correlating with allelic bias in transcription factor binding solely under nitrogen scarcity, where the majority of these transcription factors orchestrates the nitrogen catabolite repression regulatory pathway and demonstrates a cis × environment- specific response. Our approach allowed us to find cis variants modulating gene expression, chromatin accessibility, and allelic differences in transcription factor binding in response to low nitrogen culture conditions. IMPORTANCE Historically, coding variants were prioritized when searching for causal mechanisms driving adaptation of natural populations to stressful environments. However, the recent focus on noncoding variants demonstrated their ubiquitous role in adaptation. Here, we performed genome-wide regulatory variation profiles between two divergent yeast strains when facing nitrogen nutritional stress. The open chromatin availability of several regulatory regions changes in response to nitrogen scarcity. Importantly, we describe regulatory events that deviate between strains. Our results demonstrate a widespread variation in gene expression regulation between naturally occurring populations in response to stressful environments.

Original languageEnglish
Article numbere00466-21
Issue number4
Publication statusPublished - Jul 2021


  • Allele-specific
  • ATAC-seq
  • Fermentation
  • Gene regulation
  • Genetics
  • Natural variation
  • Nitrogen
  • Regulatory divergence
  • Wine
  • Yeast

ASJC Scopus subject areas

  • Microbiology
  • Ecology, Evolution, Behavior and Systematics
  • Biochemistry
  • Physiology
  • Modelling and Simulation
  • Molecular Biology
  • Genetics
  • Computer Science Applications


Dive into the research topics of 'Uncovering divergence in gene expression regulation in the adaptation of yeast to nitrogen scarcity'. Together they form a unique fingerprint.

Cite this