Reference - Detail
|Author||Mizuki F, Tanaka A, Hirose Y, Ohkuma Y.|
|Title||The HIRA complex subunit Hip3 plays important roles in the silencing of meiosis-specific genes in Schizosaccharomyces pombe.|
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.
METHODOLOGY/PRINCIPAL FINDINGS: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.
|MeSH||Chromatin / metabolism Gene Expression Regulation, Fungal* Gene Silencing* Genes, Fungal Histones / chemistry* Histones / metabolism Meiosis* Models, Genetic Molecular Chaperones / genetics* Molecular Chaperones / physiology Mutation Phosphorylation Plasmids / metabolism Schizosaccharomyces / genetics* Schizosaccharomyces / metabolism* Schizosaccharomyces pombe Proteins / genetics* Schizosaccharomyces pombe Proteins / physiology Temperature Transcription, Genetic|
|WOS Category||BIOCHEMISTRY & MOLECULAR BIOLOGY|
|Yeast||genome library (pTN-L1)|