title: Overlapping Functions between SWR1 Deletion and H3K56 Acetylation in Candida albicans.
abstract: Nucleosome destabilization by histone variants and modifications has been implicated in the epigenetic regulation of gene expression, with the histone variant H2A.Z and acetylation of H3K56 (H3K56ac) being two examples. Here we find that deletion of SWR1, the major subunit of the SWR1 complex depositing H2A.Z into chromatin in exchange for H2A, promotes epigenetic white-opaque switching in Candida albicans. We demonstrate through nucleosome mapping that SWR1 is required for proper nucleosome positioning on the promoter of WOR1, the master regulator of switching, and that its effects differ in white and opaque cells. Furthermore, we find that H2A.Z is enriched adjacent to nucleosome-free regions at the WOR1 promoter in white cells, suggesting a role in the stabilization of a repressive chromatin state. Deletion of YNG2, a subunit of the NuA4 H4 histone acetyltransferase (HAT) that targets SWR1 activity through histone acetylation, produces a switching phenotype similar to that of swr1, and both may act downstream of the GlcNAc signaling pathway. We further uncovered a genetic interaction between swr1 and elevated H3K56ac with the discovery that the swr1 deletion mutant is highly sensitive to nicotinamide. Our results suggest that the interaction of H2A.Z and H3K56ac regulates epigenetic switching at the nucleosome level, as well as having global effects.
authors: Department of Biological Chemistry, University of California, Irvine, Irvine, California, USA.
authors: Zhiyun
authors: Z
authors: Guan
authors: Department of Biological Chemistry, University of California, Irvine, Irvine, California, USA h4liu@uci.edu.
authors: Haoping
authors: H
authors: Liu
mesh_terms: D000107:Acetylation; D002176:Candida albicans / Q000235:genetics / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D009707:Nucleosomes / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D020365:RNA Helicases / Q000235:genetics / Q000378:metabolism*
chemical_list: D005656:Fungal Proteins; D006657:Histones; D009707:Nucleosomes; D051548:Histone Acetyltransferases; D020365:RNA Helicases