title: Fission yeast Iec1-ino80-mediated nucleosome eviction regulates nucleotide and phosphate metabolism.
abstract: Ino80 is an ATP-dependent nucleosome-remodeling enzyme involved in transcription, replication, and the DNA damage response. Here, we characterize the fission yeast Ino80 and find that it is essential for cell viability. We show that the Ino80 complex from fission yeast mediates ATP-dependent nucleosome remodeling in vitro. The purification of the Ino80-associated complex identified a highly conserved complex and the presence of a novel zinc finger protein with similarities to the mammalian transcriptional regulator Yin Yang 1 (YY1) and other members of the GLI-Krüppel family of proteins. Deletion of this Iec1 protein or the Ino80 complex subunit arp8, ies6, or ies2 causes defects in DNA damage repair, the response to replication stress, and nucleotide metabolism. We show that Iec1 is important for the correct expression of genes involved in nucleotide metabolism, including the ribonucleotide reductase subunit cdc22 and phosphate- and adenine-responsive genes. We find that Ino80 is recruited to a large number of promoter regions on phosphate starvation, including those of phosphate- and adenine-responsive genes that depend on Iec1 for correct expression. Iec1 is required for the binding of Ino80 to target genes and subsequent histone loss at the promoter and throughout the body of these genes on phosphate starvation. This suggests that the Iec1-Ino80 complex promotes transcription through nucleosome eviction.
authors.affiliation: Chromatin and Gene Expression, Babraham Institute, Babraham, Cambridge CB22 3AT, UK.
authors.forename: Cassandra Justine
authors.initials: CJ
authors.lastname: Hogan
authors.forename: Sofia
authors.initials: S
authors.lastname: Aligianni
authors.forename: Mickaël
authors.initials: M
authors.lastname: Durand-Dubief
authors.forename: Jenna
authors.initials: J
authors.lastname: Persson
authors.forename: William R
authors.initials: WR
authors.lastname: Will
authors.forename: Judith
authors.initials: J
authors.lastname: Webster
authors.forename: Linda
authors.initials: L
authors.lastname: Wheeler
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Mathews
authors.forename: Sarah
authors.initials: S
authors.lastname: Elderkin
authors.forename: David
authors.initials: D
authors.lastname: Oxley
authors.forename: Karl
authors.initials: K
authors.lastname: Ekwall
authors.forename: Patrick Daniel
authors.initials: PD
authors.lastname: Varga-Weisz
mesh_terms: D000225:Adenine / Q000378:metabolism; D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins / Q000378:metabolism; D004249:DNA Damage; D015966:Gene Expression Regulation, Fungal; D046228:Microarray Analysis; D008969:Molecular Sequence Data; D009707:Nucleosomes / Q000378:metabolism*; D009711:Nucleotides / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016335:Zinc Fingers
chemical_list: D018797:Cell Cycle Proteins; C547064:Iec1 protein, S pombe; C547063:Ino80 protein, S pombe; D009707:Nucleosomes; D009711:Nucleotides; D010710:Phosphates; D029702:Schizosaccharomyces pombe Proteins; D014157:Transcription Factors; C080926:cdc22 protein, S pombe; D000225:Adenine