title: The glucanosyltransferase Gas1 functions in transcriptional silencing.
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.
authors.affiliation: Section of Molecular Biology, Division of Biological Sciences, UCSD Moores Cancer Center, University of California at San Diego, La Jolla, CA 92093-0347, USA.
authors.forename: Melissa R
authors.initials: MR
authors.lastname: Koch
authors.forename: Lorraine
authors.initials: L
authors.lastname: Pillus
mesh_terms: D002473:Cell Wall / Q000235:genetics; D002843:Chromatin / Q000378:metabolism; D004275:DNA, Ribosomal / Q000235:genetics; D017353:Gene Deletion; D020868:Gene Silencing; D005800:Genes, Fungal; D004693:Glucan Endo-1,3-beta-D-Glucosidase / Q000378:metabolism*; D006655:Histone Deacetylases / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000201:enzymology* / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000378:metabolism; D056565:Sirtuin 2; D037761:Sirtuins / Q000378:metabolism; D016615:Telomere; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques
chemical_list: D002843:Chromatin; D004275:DNA, Ribosomal; C066709:GAS1 protein, S cerevisiae; D008562:Membrane Glycoproteins; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D004693:Glucan Endo-1,3-beta-D-Glucosidase; C087778:SIR2 protein, S cerevisiae; D056565:Sirtuin 2; D037761:Sirtuins; D006655:Histone Deacetylases