Alternative TSS use is widespread in Cryptococcus fungi in response to environmental cues and regulated genome-wide by the transcription factor Tur1.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101183755 Publication Model: eCollection Cited Medium: Internet ISSN: 1545-7885 (Electronic) Linking ISSN: 15449173 NLM ISO Abbreviation: PLoS Biol Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science, [2003]-

Fungal Proteins*/genetics ; Fungal Proteins*/metabolism ; Gene Expression Regulation, Fungal* ; Transcription Factors*/metabolism ; Transcription Factors*/genetics ; Transcription Initiation Site* ; Genome, Fungal*; Cryptococcus/genetics ; Cryptococcus/pathogenicity ; Cryptococcus/metabolism ; Cryptococcus neoformans/genetics ; Cryptococcus neoformans/pathogenicity ; Cryptococcus neoformans/metabolism ; Macrophages/microbiology ; Macrophages/metabolism ; Animals ; Mice ; Virulence/genetics ; Phagocytosis/genetics

Alternative transcription start site (TSS) usage regulation has been identified as a major means of gene expression regulation in metazoans. However, in fungi, its impact remains elusive as its study has thus far been restricted to model yeasts. Here, we first re-analyzed TSS-seq data to define genuine TSS clusters in 2 species of pathogenic Cryptococcus. We identified 2 types of TSS clusters associated with specific DNA sequence motifs. Our analysis also revealed that alternative TSS usage regulation in response to environmental cues is widespread in Cryptococcus, altering gene expression and protein targeting. Importantly, we performed a forward genetic screen to identify a unique transcription factor (TF) named Tur1, which regulates alternative TSS (altTSS) usage genome-wide when cells switch from exponential phase to stationary phase. ChiP-Seq and DamID-Seq analyses suggest that at some loci, the role of Tur1 might be direct. Tur1 has been previously shown to be essential for virulence in C. neoformans. We demonstrated here that a tur1Δ mutant strain is more sensitive to superoxide stress and phagocytosed more efficiently by macrophages than the wild-type (WT) strain.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Dang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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0 (Fungal Proteins)
0 (Transcription Factors)

Date Created: 20240725 Date Completed: 20240806 Latest Revision: 20240808

20240808

PMC11302930

10.1371/journal.pbio.3002724

39052688