Transcription Factor Substitution during the Evolution of Fungal Ribosome Regulation

Abstract

Coordinated ribosomal protein (RP) gene expression is crucial for cellular viability, but the transcriptional network controlling this regulon has only been well characterized in the yeast Saccharomyces cerevisiae. We have used whole-genome transcriptional and location profiling to establish that, in Candida albicans, the RP regulon is controlled by the Myb domain protein Tbf1 working in conjunction with Cbf1. These two factors bind both the promoters of RP genes and the rDNA locus; Tbf1 activates transcription at these loci and is essential. Orthologs of Tbf1 bind TTAGGG telomeric repeats in most eukaryotes, and TTAGGG cis-elements are present upstream of RP genes in plants and fungi, suggesting that Tbf1 was involved in both functions in ancestral eukaryotes. In all Hemiascomycetes, Rap1 substituted Tbf1 at telomeres and, in the S. cerevisiae lineage, this substitution also occurred independently at RP genes, illustrating the extreme adaptability and flexibility of transcriptional regulatory networks.

Gene duplication and the evolution of ribosomal protein gene regulation in yeast

“…This supports the role of Ifh1 in regulating RP gene expression in each of these species. As previously shown, the outgroup species C. albicans has a different cis-regulatory organization, dominated by binding sites for Tbf1 and Cbf1 and lacking directly discernible IFHL sites (5). Because the Ifh1/Fhl1 complex is physically associated with RP gene promoters in C. albicans (6), there are two possibilities for this discrepancy: (1) Fhl1 and Ifh1 bind indirectly through the Tbf1 protein (6), or (2) the Fhl1 protein recognizes a variant site, similar to the Tbf1 consensus (1,4).…”

Cis- and trans-regulatory divergence between progenitor species determines gene-expression novelty in Arabidopsis allopolyploids

“…As examples, ribosomal proteins are significantly enriched in the compensating cis and trans genes (P = 2.7e-05). In yeast, cis elements of ribosomal protein genes are highly divergent between Saccharomyces cerevisiae and Candida albicans 38 . Moreover, transcription factors affect expression evolution of ribosomal proteins 39 .…”

Rearrangements of the transcriptional regulatory networks of metabolic pathways in fungi

“…Analysis of the ICRE element across the fungal phylogeny shows that indeed, it is enriched in the peroxisomal and lipid utilization regulons in many species but the association with genes involved in fatty-acid breakdown is mostly absent in the S. cerevisiae branch (Figure 1a). The Ino2/4 heterodimer was suspected to regulate ribosomal protein (RP) genes through an element resembling the ICRE but this hypothesis was invalidated in a recent study that identified Cbf1 as the TF-binding RP CACGTG elements [22 ]. It is thus likely that the Ino2/4 complex has conserved its function in the regulation of phosphatidylinositol and phosphatidyl-choline synthesis pathways, but in addition it appears to regulate targets involved in beta-oxidation and peroxisomal biogenesis in many fungal species.…”

“…cerevisiae the regulatory circuit controlling the expression of ribosomal proteins consists of the generalist myb-domain containing transcription factor Rap1p together with the high-mobility group protein Hmo1p and a condition-sensitive switch complex made up of Ifh1 and Fhl1 [47][48][49][50][51]. In C. albicans, the Ifh1/Fhl1 switch appears to be conserved, but the key DNA-binding element of the circuit is the myb-domain protein Tbf1 ( [22 ] Lavoie et al, submitted) ( Figure 2c). As well, while the Ifh1/Fhl1 complex has a DNA-binding target (the IFHL box) in S. cerevisiae, there is no evidence for this motif in C. albicans, suggesting that all the DNA targeting function of the circuit is supplied by the Tbf1 cis-regulatory motifs.…”

“…A well characterized example of comparative genomics applied to gene expression evolution is mating type identity that is controlled by distinct circuits with identical logic in S. cerevisiae and C. albicans [19 ]. Also, ChIP-CHIP analysis of filamentous growth regulators in related Saccharomyces species [20 ], of the Mcm1 factor in three fungal species [21 ] and of ribosomal regulators in C. albicans [22 ] showed that transcriptional networks are extremely plastic.…”