Abstract
We describe a fluorescent reporter system that exploits the functional genomic tools available in budding yeast to systematically assess consequences of genetic perturbations on gene expression. We used our Reporter-Synthetic Genetic Array (R-SGA) method to screen for regulators of core histone gene expression. We discovered that the histone chaperone Rtt106 functions in a pathway with two other chaperones, Asf1 and the HIR complex, to create a repressive chromatin structure at core histone promoters. We found that activation of histone (HTA1) gene expression involves both relief of Rtt106-mediated repression by the activity of the histone acetyltransferase Rtt109 and restriction of Rtt106 to the promoter region by the bromodomain-containing protein Yta7. We propose that the maintenance of Asf1/HIR/Rtt106-mediated repressive chromatin domains is the primary mechanism of cell-cycle regulation of histone promoters. Our data suggest that this pathway may represent a chromatin regulatory mechanism that is broadly used across the genome.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Cycle Proteins / metabolism
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Chromosomal Proteins, Non-Histone / genetics
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Chromosomal Proteins, Non-Histone / metabolism
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Gene Expression Regulation*
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Genes, Reporter
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Genome, Fungal
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Genomics / methods
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Histone Acetyltransferases / genetics
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Histone Acetyltransferases / metabolism
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Histones / genetics
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Histones / metabolism
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Histones / physiology*
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Molecular Chaperones / genetics
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Molecular Chaperones / metabolism
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Molecular Chaperones / physiology*
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Nuclear Proteins / genetics
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Promoter Regions, Genetic
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Repressor Proteins / genetics
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Saccharomyces cerevisiae / genetics
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Saccharomyces cerevisiae Proteins / genetics
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Saccharomyces cerevisiae Proteins / metabolism
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Saccharomyces cerevisiae Proteins / physiology*
Substances
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ASF1 protein, S cerevisiae
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Cell Cycle Proteins
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Chromosomal Proteins, Non-Histone
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HIR1 protein, S cerevisiae
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Histones
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Molecular Chaperones
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Nuclear Proteins
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Repressor Proteins
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Rtt106 protein, S cerevisiae
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Saccharomyces cerevisiae Proteins
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YTA7 protein, S cerevisiae
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Histone Acetyltransferases
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Rtt109 protein, S cerevisiae