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Perinuclear localization of chromatin facilitates transcriptional silencing

An Erratum to this article was published on 01 October 1998

Abstract

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 genes1,2,3,4. 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.

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Figure 1: GBD hybrids localized by indirect immunofluorescence.
Figure 2: Targeted silencing by GBD–YIP1.
Figure 3: Several membrane protein hybrids give targeted silencing.
Figure 4: Overexpression of SIR3 and SIR4 improves silencing in strains with defective silencers.

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Acknowledgements

We thank D. Gallwitz for communicating unpublished results; N. Dean, H. Park, S. Marcand, D. Shore and R. Brazas for plasmids and strains; and N. Dean, A. Mook and C. Dingwall for advice and comments. This work was supported by a grant from the NIH.

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Correspondence to Rolf Sternglanz.

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Andrulis, E., Neiman, A., Zappulla, D. et al. Perinuclear localization of chromatin facilitates transcriptional silencing. Nature 394, 592–595 (1998). https://doi.org/10.1038/29100

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