Abstract
BackgroundThe 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 FindingsIn 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.ConclusionsTaken 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.
Highlights
In eukaryotes, genomic information is hierarchically compacted into chromatin
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
SPCC663.14c+ was identified as a meiosis-specific gene by screening for genes that are repressed during mitosis and induced upon nitrogen starvation according to the S. pombe gene DB [19]. leu2 ura2 cells transformed with the pSP1-meiURA4 plasmid grew on minimal medium (MM) plates containing uracil but not on plates without uracil
Summary
Genomic information is hierarchically compacted into chromatin. it is necessary to open the chromatin structure upon the stimulation of gene expression [1,2]. The regulation of gene expression is required for proper growth responses to environmental changes [3,4]. RNA polymerase II (Pol II) catalyzes the transcription of all the protein-coding genes. Pol II and five general transcription factors (TFIIB, -D, -E, -F and -H) form a preinitiation complex (PIC) on promoter DNA [5,6]. 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 hip mutant was isolated via discovery of a defect in the transcriptional repression of meiosis-specific genes. Hip is a subunit of the HIRA (histone regulatory complex A) complex, which consists of four subunits (Hip, Hip, Hip and Slm9) and acts as a histone chaperone that is independent of DNA replication
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