Stable, epigenetic inactivation of gene expression by silencing complexes involves a specialized heterochromatin structure, but the kinetics and pathway by which euchromatin is converted to the stable heterochromatin state are poorly understood. Induction of heterochromatin in Saccharomyces cerevisiae by expression of the silencing protein Sir3 results in rapid loss of histone acetylation, whereas removal of euchromatic histone methylation occurs gradually through several cell generations. Unexpectedly, Sir3 binding and the degree of transcriptional repression gradually increase for 3-5 cell generations, even though the intracellular level of Sir3 remains constant. Strains lacking Sas2 histone acetylase or the histone methylases that modify lysines 4 (Set1) or 79 (Dot1) of H3 display accelerated Sir3 accumulation at HMR or its spreading away from the telomere, suggesting that these histone modifications exert distinct inhibitory effects on heterochromatin formation. These findings suggest an ordered pathway of heterochromatin assembly, consisting of an early phase, driven by active enzymatic removal of histone acetylation and resulting in incomplete transcriptional silencing, followed by a slower maturation phase, in which gradual loss of histone methylation enhances Sir association and silencing. Thus, the transition between euchromatin and heterochromatin is gradual and requires multiple cell division cycles.
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Evidence ID | Analyze ID | Gene/Complex | Systematic Name/Complex Accession | Qualifier | Gene Ontology Term ID | Gene Ontology Term | Aspect | Annotation Extension | Evidence | Method | Source | Assigned On | Reference |
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Evidence ID | Analyze ID | Gene | Gene Systematic Name | Phenotype | Experiment Type | Experiment Type Category | Mutant Information | Strain Background | Chemical | Details | Reference |
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Evidence ID | Analyze ID | Gene | Gene Systematic Name | Disease Ontology Term | Disease Ontology Term ID | Qualifier | Evidence | Method | Source | Assigned On | Reference |
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Evidence ID | Analyze ID | Regulator | Regulator Systematic Name | Target | Target Systematic Name | Direction | Regulation of | Happens During | Regulator Type | Direction | Regulation Of | Happens During | Method | Evidence | Strain Background | Reference |
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Site | Modification | Modifier | Source | Reference |
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Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Allele | Assay | Annotation | Action | Phenotype | SGA score | P-value | Source | Reference | Note |
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Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Assay | Annotation | Action | Modification | Source | Reference | Note |
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Complement ID | Locus ID | Gene | Species | Gene ID | Strain background | Direction | Details | Source | Reference |
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Evidence ID | Analyze ID | Dataset | Description | Keywords | Number of Conditions | Reference |
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Evidence ID | Analyze ID | File | Description |
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