Biology subjects

Vande Zande, P.

Publications and source records attributed to Vande Zande, P..

2 recordsLinked to original sources

bioRxiv2023

Active compensation for changes in TDH3 expression mediated by direct regulators of TDH3 in Saccharomyces cerevisiae

Genetic networks are surprisingly robust to perturbations caused by new mutations. This robustness is conferred in part by compensation for loss of a genes activity by genes with overlapping functions, such as paralogs. Compensation occurs passively when the normal activity of one paralog can compensate for the loss of the other, or actively when a change in one paralogs expression, localization, or activity is required to compensate for loss of the other. The mechanisms of active compensation remain poorly understood in most cases. Here we investigate active compensation for the loss or reduction in expression of the Saccharomyces cerevisiae gene TDH3 by its paralogs TDH1 and TDH2. TDH1 and TDH2 are upregulated in a dose-dependent manner in response to reductions in TDH3 by a mechanism requiring the shared transcriptional regulators Gcr1p and Rap1p. Other glycolytic genes regulated by Rap1p and Gcr1p show changes in expression similar to TDH2, suggesting that the active compensation by TDH3 paralogs is part of a broader homeostatic response mediated by shared transcriptional regulators.

cell biology↗

bioRxiv2021

Mutational sources of trans-regulatory variation affecting gene expression in Saccharomyces cerevisiae

Heritable variation in a genes expression arises from mutations impacting cis- and trans-acting components of its regulatory network, with expression variation often derived from trans-regulatory mutations within species. Here, we investigate how trans-regulatory mutations are distributed within the genome and within a gene regulatory network by identifying and characterizing 69 mutations with trans-regulatory effects on expression of the same focal gene in Saccharomyces cerevisiae. Relative to 1766 mutations without effects on expression of this focal gene, we found that these trans-regulatory mutations were enriched in coding sequences of transcription factors previously predicted to regulate expression of the focal gene. However, over 90% of the trans-regulatory mutations identified mapped to other types of genes involved in diverse biological processes including chromatin state, metabolism and signal transduction. Finally, we find that the genomic distribution of these new regulatory mutations significantly overlaps with the genomic distribution of trans-regulatory variants segregating within S. cerevisiae.

genetics↗