Perinuclear localization of chromatin facilitates transcriptional silencing

Erik D. Andrulis, Aaron M. Neiman, David C. Zappulla and Rolf Sternglanz ()
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Erik D. Andrulis: State University of New York at Stony Brook
Aaron M. Neiman: State University of New York at Stony Brook
David C. Zappulla: State University of New York at Stony Brook
Rolf Sternglanz: State University of New York at Stony Brook

Nature, 1998, vol. 394, issue 6693, 592-595

Abstract: 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.

Date: 1998
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DOI: 10.1038/29100

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