Merge and separation of NuA4 and SWR1 complexes control cell fate plasticity in Candida albicans

Xiongjun Wang,Peng Chang,Haoping Liu,Jiangye Chen,Hongyu Wu,Wencheng Zhu

doi:10.1038/s41421-018-0043-0

Abstract

Phenotypic plasticity is common in development. Candida albicans, a polymorphic fungal pathogen of humans, possesses the unique ability to achieve rapid and reversible cell fate between unicellular form (yeast) and multicellular form (hypha) in response to environmental cues. The NuA4 histone acetyltransferase activity and Hda1 histone deacetylase activity have been reported to be required for hyphal initiation and maintenance. However, how Hda1 and NuA4 regulate hyphal elongation is not clear. NuA4 histone acetyltransferase and SWR1 chromatin remodeling complexes are conserved from yeast to human, which may have merged together to form a larger TIP60 complex since the origin of metazoan. In this study, we show a dynamic merge and separation of NuA4 and SWR1 complexes in C. albicans. NuA4 and SWR1 merge together in yeast state and separate into two distinct complexes in hyphal state. We demonstrate that acetylation of Eaf1 K173 controls the interaction between the two complexes. The YEATS domain of Yaf9 in C. albicans can recognize an acetyl-lysine of the Eaf1 and mediate the Yaf9-Eaf1 interaction. The reversible acetylation and deacetylation of Eaf1 by Esa1 and Hda1 control the merge and separation of NuA4 and SWR1, and this regulation is triggered by Brg1 recruitment of Hda1 to chromatin in response nutritional signals that sustain hyphal elongation. We have also observed an orchestrated promoter association of Esa1, Hda1, Swr1, and H2A.Z during the reversible yeast–hyphae transitions. This is the first discovery of a regulated merge of the NuA4 and SWR1 complexes that controls cell fate determination and this regulation may be conserved in polymorphic fungi.

Highlights

Cell fate plasticity is common in a broad range of biological events from embryo development to tissue regeneration
We find that Eaf1K173R mutant cells sustained hyphal development in YPD (Fig. 6d and Supplementary Fig. S4), bypassing the requirement of the nutritional signals required for hyphal elongation, whereas Eaf1K173Q mutant cells failed to sustain hyphae in all hyphal-inducing media tested (Fig. 6d and Supplementary Fig. S4)
We demonstrate a dynamic merge and separation of NuA4 and SWR1 complexes during transition between yeast growth and hyphal development in C. albicans

Summary

Introduction

Cell fate plasticity is common in a broad range of biological events from embryo development to tissue regeneration. Reprogramming of cell fate is regulated in multiple layers including epigenetic modifications at both DNA and chromatin levels[1,2]. NuA4 (nucleosome acetyltransferase of H4) is a multisubunit HAT (histone acetyltransferase) complex that is highly conserved in eukaryotes and has important roles in cell cycle progression, cell transformation, development, apoptosis, transcription, and DNA repair[3,4,5,6,7,8,9]. Saccharomyces cerevisiae NuA4 is composed of 13 subunits[9,10], including the essential acetyltransferase subunit Esa[111–13] and the platform protein Eaf[1], which has a crucial function in NuA4 complex integrity and assembly[14,15] (Fig.1a). SWR1 is composed of 14 subunits organized into discrete functional modules

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Results

Conclusion