Perinuclear localization of chromatin facilitates transcriptional silencing

• Published in: Nature (London) Vol. 394; no. 6693; pp. 592 - 595
• Main Authors: Sternglanz, Rolf, Andrulis, Erik D, Neiman, Aaron M, Zappulla, David C
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 06.08.1998; Nature Publishing Group
• Subjects: Binding Sites; Biochemistry; Biological and medical sciences; Cell Nucleus - metabolism; Chromatin - metabolism; Deoxyribonucleic acid; DNA; DNA, Fungal - metabolism; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Fundamental and applied biological sciences. Psychology; Fungal Proteins - genetics; Fungal Proteins - metabolism; Gene Expression Regulation, Fungal; Gene Targeting; Genes; Genes, Fungal - genetics; Genes, Mating Type, Fungal; Histone Deacetylases; Hybrids; Membrane Proteins - genetics; Membrane Proteins - metabolism; Molecular and cellular biology; Molecular genetics; Nuclear Envelope - metabolism; Proteins; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae Proteins; Silent Information Regulator Proteins, Saccharomyces cerevisiae; Sirtuin 2; Sirtuins; Trans-Activators - genetics; Trans-Activators - metabolism; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription, Genetic; Transcription. Transcription factor. Splicing. Rna processing; Yeast; Fungi; Chromatin; Regulation(control); Yeast; Transcription; Ascomycetes; Localization; Saccharomyces cerevisiae; Thallophyta
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/29100

Transcriptional silencing in Saccharomyces cerevisiae at the HM mating-type loci and telomeres occurs through the formation of a heterochromatin-like structure. HM silencing is regulated by cis-acting elements, termed silencers, and by trans-acting factors that bind to the silencers. These factors attract the four SIR (silent information regulator) proteins, three of which (SIR2-4) spread from the silencers to alter chromatin, hence silencing nearby genes. We show here that an HMR locus with a defective silencer can be silenced by anchoring the locus to the nuclear periphery. This was accomplished by fusing integral membrane proteins to the GAL4 DNA-binding domain and overproducing the hybrid proteins, causing them to accumulate in the endoplasmic reticulum and the nuclear membrane. We expressed the hybrid proteins in a strain carrying an HMR silencer with GAL4-binding sites (UASG) replacing silencer elements, causing the silencer to become anchored to the nuclear periphery and leading to silencing of a nearby reporter gene. This silencing required the hybrids of the GAL4 DNA-binding domain with membrane proteins, the UASG sites and the SIR proteins. Our results indicate that perinuclear localization helps to establish transcriptionally silent chromatin.