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PMID: 19541632 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

The glucanosyltransferase Gas1 functions in transcriptional silencing.

Koch MR, Pillus L

Abstract

Transcriptional silencing is a crucial process that is mediated through chromatin structure. The histone deacetylase Sir2 silences genomic regions that include telomeres, ribosomal DNA (rDNA) and the cryptic mating-type loci. Here, we report an unsuspected role for the enzyme Gas1 in locus-specific transcriptional silencing. GAS1 encodes a beta-1,3-glucanosyltransferase previously characterized for its role in cell wall biogenesis. In gas1 mutants, telomeric silencing is defective and rDNA silencing is enhanced. We show that the catalytic activity of Gas1 is required for normal silencing, and that Gas1's role in silencing is distinct from its role in cell wall biogenesis. Established hallmarks of silent chromatin, such as Sir2 and Sir3 binding, H4K16 deacetylation, and H3K56 deacetylation, appear unaffected in gas1 mutants. Thus, another event required for telomeric silencing must be influenced by GAS1. Because the catalytic activity of Gas1 is required for telomeric silencing, Gas1 localizes to the nuclear periphery, and Gas1 and Sir2 physically interact, we propose a model in which carbohydrate modification of chromatin components provides a new regulatory element that may be critical for chromatin function but which is virtually unexplored in the current landscape of chromatin analysis.

MeSH Terms
Cell Wall/genetics Chromatin/metabolism DNA, Ribosomal/genetics Gene Deletion Gene Silencing Genes, Fungal Glucan Endo-1,3-beta-D-Glucosidase/metabolism Histone Deacetylases/metabolism Membrane Glycoproteins/metabolism Protein Binding Saccharomyces cerevisiae/cytology,enzymology,genetics Saccharomyces cerevisiae Proteins/metabolism Silent Information Regulator Proteins, Saccharomyces cerevisiae/metabolism Sirtuin 2 Sirtuins/metabolism Telomere Transcription, Genetic Two-Hybrid System Techniques
Chemicals
Chromatin DNA, Ribosomal GAS1 protein, S cerevisiae Membrane Glycoproteins Saccharomyces cerevisiae Proteins Silent Information Regulator Proteins, Saccharomyces cerevisiae Glucan Endo-1,3-beta-D-Glucosidase SIR2 protein, S cerevisiae Sirtuin 2 Sirtuins Histone Deacetylases
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Koch Melissa R
Section of Molecular Biology, Division of Biological Sciences, UCSD Moores Cancer Center, University of California at San Diego, La Jolla, CA 92093-0347, USA.
Pillus Lorraine
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
Published
2009-07-07
Epub
2009-00-16
Pages
11224-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC2708717
Subset
IM
Corrections
CommentIn
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