Histone binding of ASF1 is required for fruiting body development but not for genome stability in the filamentous fungus \(\textit {Sordaria macrospora}\)

  • he highly conserved eukaryotic histone chaperone ASF1 is involved in the assembly and disassembly of nucleosomes during transcription, DNA replication, and repair. It was the first chaperone discovered to be involved in all three of these processes. The filamentous fungus \(\textit {Sordaria macrospora}\) is one of only two multicellular organisms where \(\it asf1\) deletions are viable, which makes it useful for \(\it in vivo\) analysis of this central regulator of eukaryotic chromatin structure. Deletion of \(\it asf1\) in \(\it S. macrospora\) leads to sterility, a reduction of DNA methylation, and upregulation of genes that are usually weakly expressed in the wild type. Here, we focused on the functions of the highly conserved core and the divergent C-terminal tail of ASF1, studied the effects of ASF1 on histone modifications, and tested its relevance for genomic stability. By co-immunoprecipitation and complementation analysis, we showed that substitutions of amino acid V94 or truncations of the C-terminal tail abolish histone binding and do not complement the sterile mutant phenotype. \(\Delta\)asf1 is sensitive to the DNA-damaging agent methyl methanesulfonate, while complementation strains, even those with non-histone-binding variants, regain wild type-like resistance. The histone marks H3K27me3 and H3K56ac were shown to be influenced by the histone-binding capability of ASF1. To aid in subsequent analyses, we generated a chromosome-resolved genome assembly of \(\it S. macrospora\). By using Hi-C, we detected a tandem duplication of around 600 kb on chromosome 2 in the mutant. Crossing experiments indicated linkage between the viability of \(\Delta\)asf1 strains and the presence of the duplication.

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Author:Jan BreuerGND, Tobias BuscheGND, Jörn KalinowskiGND, Minou NowrousianORCiDGND
Parent Title (English):mBio
Publisher:American Society for Microbiology
Place of publication:Washington, DC
Document Type:Article
Date of Publication (online):2024/03/20
Date of first Publication:2023/12/19
Publishing Institution:Ruhr-Universität Bochum, Universitätsbibliothek
Tag:Open Access Fonds
ASF1; Hi-C; filamentous fungi; fruiting body formation; histone chaperone; multicelllular development
First Page:1
Last Page:24
Article Processing Charge funded by the Deutsche Forschungsgemeinschaft (DFG) and the Open Access Publication Fund of Ruhr-Universität Bochum.
Institutes/Facilities:Lehrstuhl für Molekulare und Zelluläre Botanik
Dewey Decimal Classification:Naturwissenschaften und Mathematik / Biowissenschaften, Biologie, Biochemie
open_access (DINI-Set):open_access
faculties:Fakultät für Biologie und Biotechnologie
Licence (English):License LogoCreative Commons - CC BY 4.0 - Attribution 4.0 International