The YEATS Domain Histone Crotonylation Readers Control Virulence-Related Biology of a Major Human Pathogen

Abstract

Summary: Identification of multiple histone acylations diversifies transcriptional control by metabolism, but their functions are incompletely defined. Here we report evidence of histone crotonylation in the human fungal pathogen Candida albicans. We define the enzymes that regulate crotonylation and show its dynamic control by environmental signals: carbon sources, the short-chain fatty acids butyrate and crotonate, and cell wall stress. Crotonate regulates stress-responsive transcription and rescues C. albicans from cell wall stress, indicating broad impact on cell biology. The YEATS domain crotonylation readers Taf14 and Yaf9 are required for C. albicans virulence, and Taf14 controls gene expression, stress resistance, and invasive growth via its chromatin reader function. Blocking the Taf14 C terminus with a tag reduced virulence, suggesting that inhibiting Taf14 interactions with chromatin regulators impairs function. Our findings shed light on the regulation of histone crotonylation and the functions of the YEATS proteins in eukaryotic pathogen biology and fungal infections. : Diverse histone acylations expand functional linkages among metabolism, gene regulation, and cellular responses. Wang et al. report that metabolic and stress cues dynamically control histone crotonylation in the human commensal and pathogen Candida albicans and show the requirement for crotonylation readers in pathogenesis-related pathways and mammalian virulence. Keywords: histone crotonylation, YEATS domain readers, Taf14, Yaf9, Candida albicans, metabolism, fungal pathogens, cell wall