Regulation of the Growth‐Inhibitory Activity of Fhl1 via Interaction With Ifh1 and Crf1 at the Ribosomal Protein Gene Promoters in Saccharomyces cerevisiae

The transcription factor Fhl1, which binds to the promoters of the ribosomal protein genes (RPGs) in Saccharomyces cerevisiae, promotes transcription by recruiting the transcription activator Ifh1 under nutrient-rich conditions. During starvation, Ifh1 dissociates from the RPG promoter, and the transcriptional repressor Crf1 binds to Fhl1 instead of Ifh1, thereby suppressing transcription. However, the lethality of the ifh1Δ strain was suppressed by deletion of FHL1, suggesting that Ifh1 has essential functions beyond transcriptional activation. Detailed analyses using various deletion mutants of Fhl1 and Ifh1 revealed that the lethality of the ifh1Δ strain is suppressed by mutation of the forkhead-associated (FHA) domain, which interacts with the forkhead-binding (FHB) domains of Ifh1 and Crf1. Inducing Fhl1-expression in ifh1Δfhl1Δ strain suppressed growth, indicating that promoter-bound Fhl1 inhibits RPG transcription via an unknown mechanism. The lethality of ifh1Δ strain was suppressed by expression of the Ifh1 FHB domain from its native promoter or by overexpression of the corresponding domain of Crf1. These findings suggest that, while Fhl1 promotes transcription by recruiting Ifh1, dissociation of Ifh1 exposes the FHA domain, which triggers growth inhibition via an unknown mechanism. Binding to the FHA domain and neutralizing its inhibitory activity may represent a key function of Ifh1.