Cross-species complementation profiling of Taf14 orthologs reveals module-specific incompatibilities in Saccharomyces cerevisiae

Abstract Eukaryotic transcription requires a dynamic chromatin structure to regulate spatial and temporal access to genetic information, a process driven by specialized complexes that modify and remodel chromatin. Fungal transcription factor Taf14 is a subunit of multiple transcription and chromatin-remodelling protein complexes. It belongs to the conserved YEATS family of acyl-lysine reader proteins, which are frequently implicated in human oncogenesis. While the YEATS family proteins are conserved throughout eukaryotes, Taf14 represents a variant found mainly in fungi. Analysis of the structural and functional conservation of Taf14 across fungal lineages revealed that the structured YEATS and ET domains maintain sequence homogeneity, while the intervening linker varies in primary sequence and length. Despite this divergence, the linker preserves a net positive charge density implicated in non-sequence-specific DNA interaction. When expressed in an S. cerevisiae taf14Δ background, the majority of ascomycete Taf14 orthologs rescued the taf14Δ phenotype, indicating functional compatibility among related yeasts. However, orthologs from Metschnikowia pulcherrima and Hanseniaspora uvarum failed to complement the loss of TAF14 , as their YEATS or linker regions rendered the proteins non-functional in S. cerevisiae . These findings demonstrate that the functional compatibility of Taf14 proteins relies on the properties of both their structured domains and intrinsically disordered linker.