title: The SAGA subunit Ada2 functions in transcriptional silencing.
abstract: The cellular role of the Ada2 coactivator is currently understood in the context of the SAGA histone acetyltransferase (HAT) complex, where Ada2 increases the HAT activity of Gcn5 and interacts with transcriptional activators. Here we report a new function for Ada2 in promoting transcriptional silencing at telomeres and ribosomal DNA. This silencing function is the first characterized role for Ada2 distinct from its involvement with Gcn5. Ada2 binds telomeric chromatin and the silencing protein Sir2 in vivo. Loss of ADA2 causes the spreading of Sir2 and Sir3 into subtelomeric regions and decreased histone H4 K16 acetylation. This previously uncharacterized boundary activity of Ada2 is functionally similar to, but mechanistically distinct from, that of the MYST family HAT Sas2. Mounting evidence in the literature indicates that boundary activities create chromosomal domains important for regulating gene expression in response to environmental changes. Consistent with this, we show that upon nutritional changes, Ada2 occupancy increases at a subtelomeric region proximal to a SAGA-inducible gene and causes derepression of a silenced telomeric reporter gene. Thus, Ada2, likely in the context of SAGA, is positioned at chromosomal termini to participate in both transcriptional repression and activation in response to nutrient signaling.
authors.affiliation: Division of Biological Sciences, University of California at San Diego, 9500 Gilman Dr., 0347, San Diego, CA 92093, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Jacobson
authors.forename: Lorraine
authors.initials: L
authors.lastname: Pillus
mesh_terms: D000107:Acetylation / Q000187:drug effects; D002244:Carbon / Q000494:pharmacology; D002843:Chromatin / Q000378:metabolism; D004275:DNA, Ribosomal / Q000378:metabolism; D017353:Gene Deletion; D020868:Gene Silencing / Q000187:drug effects; D006657:Histones / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D008954:Models, Biological; D011485:Protein Binding / Q000187:drug effects; D021122:Protein Subunits / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000378:metabolism; D056565:Sirtuin 2 / Q000378:metabolism; D016615:Telomere / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: C090575:ADA2 protein, S cerevisiae; D002843:Chromatin; D004275:DNA, Ribosomal; D006657:Histones; D021122:Protein Subunits; C084122:SIR3 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D014157:Transcription Factors; D002244:Carbon; C087778:SIR2 protein, S cerevisiae; D056565:Sirtuin 2; D008239:Lysine