N-acetylglucosamine sensing by a GCN5-related N-acetyltransferase induces transcription via chromatin histone acetylation in fungi.

Chang Su,Yang Lu,Haoping Liu

doi:10.1038/ncomms12916

Abstract

N-acetylglucosamine (GlcNAc) exists ubiquitously as a component of the surface on a wide range of cells, from bacteria to humans. Many fungi are able to utilize environmental GlcNAc to support growth and induce cellular development, a property important for their survival in various host niches. However, how the GlcNAc signal is sensed and subsequently transduced is largely unknown. Here, we identify a gene that is essential for GlcNAc signalling (NGS1) in Candida albicans, a commensal and pathogenic yeast of humans. Ngs1 can bind GlcNAc through the N-terminal β-N-acetylglucosaminidase homology domain. This binding activates N-acetyltransferase activity in the C-terminal GCN5-related N-acetyltransferase domain, which is required for GlcNAc-induced promoter histone acetylation and transcription. Ngs1 is targeted to the promoters of GlcNAc-inducible genes constitutively by the transcription factor Rep1. Ngs1 is conserved in diverse fungi that have GlcNAc catabolic genes. Thus, fungi use Ngs1 as a GlcNAc-sensor and transducer for GlcNAc-induced transcription.

Highlights

N-acetylglucosamine (GlcNAc) exists ubiquitously as a component of the surface on a wide range of cells, from bacteria to humans
From a knockout library of 674 unique genes in C. albicans[24], three mutants (nag[1], snf[4], orf19.7516 (CR_00190W)) were found to be unable to grow on GlcNAc (Fig. 1a). orf19.7516 is required for GlcNAc utilization as the orf19.7516 mutant grew well on galactose or on GlcNAc media supplemented with galactose or amino acids, similar to the GlcNAc transporter mutant ngt[1]
Extracellular GlcNAc is taken into cells using a phosphotransferase system that converts GlcNAc to GlcNAc6-PO4

Summary

Introduction

N-acetylglucosamine (GlcNAc) exists ubiquitously as a component of the surface on a wide range of cells, from bacteria to humans. Can GlcNAc induce genes for GlcNAc catabolism, it can promote C. albicans cells to undergo hyphal development[18] and phenotypic switching between two heritable cell states[19]. These morphogenesis programs of C. albicans are linked to its virulence, infection of distinct host niches and immune evasion[20,21]. Ngs[1] contains a conserved GlcNAc binding pocket at its N-terminus and a C-terminal GNAT domain; both are important for GlcNAc-induced promoter chromatin acetylation and transcription of GlcNAc catabolic genes. Ngs[1] is a novel GlcNAc signal sensor-transducer in fungi

Methods

Results

Conclusion