Consistency of gene expression and protein acetylation modification with physiological and biochemical changes responding to the deficiency of histone deacetylase 1 homolog in Monascus ruber

Abstract

Monascus species can produce several secondary metabolites (SMs), which are regulated by a complex network. Histone deacetylase 1 (Hda1) has been demonstrated as a critical regulator of SMs and developmental processes; however, little is known about Hda1 in Monascus spp. (named MrHda1). In this study, strain ΔMrHda1 was generated for phenotypic assays. The results indicated that MrHda1 inactivation led to reduced conidia and ascospores but significantly increased pigment and citrinin production. Transcriptome data showed that MrHda1 deletion upregulated the expression of most genes in the glycolytic pathway as well as the gene clusters involved in pigment and citrinin biosynthesis. Western blotting (WB) and label-free acetylome data indicated that MrHda1 deletion significantly enhanced lysine acetylation modifications on the H3 subunit and enzymes involved in the citric acid cycle. Site-directed mutation demonstrated that the production of pigments and citrinin directly correlates with the acetylation level of histone H3 lysine 18 (H3K18). These findings provide new insights into the essential functions of MrHda1 and its regulation mechanisms on the SMs.