title: The HIRA complex subunit Hip3 plays important roles in the silencing of meiosis-specific genes in Schizosaccharomyces pombe.
abstract: BACKGROUND
  The control of gene expression is essential for growth and responses to environmental changes in various organisms. It is known that some meiosis-specific genes are silenced during mitosis and expressed upon nitrogen starvation in Schizosaccharomyces pombe. When the factors responsible for this regulation were studied, a hip3 mutant was isolated via discovery of a defect in the transcriptional repression of meiosis-specific genes. Hip3 is a subunit of the HIRA (histone regulatory complex A) complex, which consists of four subunits (Hip1, Hip3, Hip4 and Slm9) and acts as a histone chaperone that is independent of DNA replication.
  
  
  RESULTS
  In a search for mutants, the meiosis-specific gene SPCC663.14c(+) was identified by screening for genes that are silenced during mitosis and induced upon nitrogen starvation. A reporter plasmid that expresses the ura4(+) gene driven by the SPCC663.14c(+) promoter was constructed. Screening for suppressor mutants was then carried out in nitrogen-rich medium without uracil. A mutant with a mutation in the hip3(+) gene was isolated and named hip3-1. This mutation alleviated the transcriptional repression of the ura4(+) gene on the reporter plasmid and of the endogenous SPCC663.14c(+) gene in the presence of nitrogen. A ChIP assay revealed that RNA polymerase II (Pol II) and TFIIE were enriched at the SPCC663.14c(+) locus, whereas the levels of histone H3 were decreased in hip3-1 cells. Intriguingly, histone H3 was heavily modified at the SPCC663.14c(+) locus in hip3-1 cells; these modifications included tri-methylation and acetylation of H3 lysine 9 (H3K9), mono-methylation of H3 arginine 2 (H3R2), and tri-methylation of H3 lysine 4 (H3K4). In addition, the tri-methylation of H3K9 and H3K4 were strongly elevated in hip3-1 mutants.
  
  
  CONCLUSIONS
  Taken together, these results indicate that Hip3 plays important roles in the control of histone modifications at meiosis-specific gene loci and induces their transcriptional repression.
authors.affiliation: Laboratory of Gene Regulation, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Mizuki
authors.forename: Aki
authors.initials: A
authors.lastname: Tanaka
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Hirose
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ohkuma
mesh_terms: D002843:Chromatin / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D020868:Gene Silencing; D005800:Genes, Fungal; D006657:Histones / Q000737:chemistry* / Q000378:metabolism; D008540:Meiosis; D008957:Models, Genetic; D018832:Molecular Chaperones / Q000235:genetics* / Q000502:physiology; D009154:Mutation; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics* / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics* / Q000502:physiology; D013696:Temperature; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; C562347:Hip3 protein, S pombe; D006657:Histones; D018832:Molecular Chaperones; D029702:Schizosaccharomyces pombe Proteins