MADS-Box Transcription Factors Regulate Dimorphic Transition and Temperature Adaptation in the Pathogenic Fungus Talaromyces marneffei [ChIP-Seq]

The dynamic transition between yeast and hyphal forms is a crucial adaptive mechanism for many human pathogenic fungi, including Talaromyces marneffei, a thermodimorphic fungus responsible for causing fatal talaromycosis globally. This study aimed to uncover the genetic mechanisms underlying the dimorphic transition in T. marneffei, focusing on the MADS-box transcription factor family. Using adaptive laboratory evolution, we identified MADS-box genes enriched in dimorphism-defective mutants, revealing a notable expansion of this gene family in T. marneffei. Phylogenetic analysis and functional genetic manipulations confirmed the involvement of mads9, mads10, and mads13 in regulating the yeast-hypha transition. Integrating RNA sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq), we demonstrated that these transcription factors target genes involved in transmembrane transport, redox processes, and cellulose binding. Our findings not only clarify the role and regulatory mechanisms of the MADS-box family in dimorphic transitions but also present a valuable strategy for identifying regulatory genes based on morphological variations and high-throughput sequencing, paving the way for further systematic genetic studies of fungal temperature adaptation. ChIP-seq and paried RNA-seq were performed on wild type PM1 strain, madsA overexpression, mads9 overexpression, and madsA knockout, and mads9 knockout strains under both mycelia and yeast conditions.