Fig. 5: Mutations in transcription factors are over-represented.

a Genes identified with three or more different compounds. Genes (8) with ontology GO:0140110 (transcription regulator activity) are shown in red. YRR1 (b) and YRM1 (c) mutation localization. Distribution of mutations in YRR1 and YRM1 across the amino acid sequence clustered in the C-terminal activation domain. d Scaffolds. Compounds used in selections resulting in YRR1 and YRM1 mutations. e YRR1 single-nucleotide mutations but not loss-of-function mutations constitutively activate transcriptional targets. RT-qPCR was utilized to monitor mRNA levels of YRR1 and YRR1 activated genes. Clones with YRR1 point mutations show increases in mRNA levels of YRR1, SNG1, FLG1, and AZR1 relative to the wild-type strain (GM), but the deletion mutant does not. In the absence of YRR1, associated genes display baseline or lower level of expression. The heatmap indicates fold change normalized to ACT1.