Rpd3-dependent boundary formation at telomeres by removal of Sir2 substrate.
Boundaries between euchromatic and heterochromatic regions until now have been associated with chromatin-opening activities. Here, we identified an unexpected role for histone deacetylation in this process. Significantly, the histone deacetylase (HDAC) Rpd3 was necessary for boundary formation in Saccharomyces cerevisiae. rpd3Delta led to silent information regulator (SIR) spreading and repression of subtelomeric genes. In the absence of a known boundary factor, the histone acetyltransferase complex SAS-I, rpd3Delta caused inappropriate SIR spreading that was lethal to yeast cells. Notably, Rpd3 was capable of creating a boundary when targeted to heterochromatin. Our data suggest a mechanism for boundary formation whereby histone deacetylation by Rpd3 removes the substrate for the HDAC Sir2, so that Sir2 no longer can produce O-acetyl-ADP ribose (OAADPR) by consumption of NAD(+) in the deacetylation reaction. In essence, OAADPR therefore is unavailable for binding to Sir3, preventing SIR propagation.
Ehrentraut
Stefan
S
Abteilung für Genetik and Abteilung für Bioinformatik, Zentrum für Medizinische Biotechnologie, Universität Duisburg-Essen, D- 45117 Essen, Germany.
Weber
Jan M
JM
Dybowski
J Nikolaj
JN
Hoffmann
Daniel
D
Ehrenhofer-Murray
Ann E
AE
D000107:Acetylation; D022041:Euchromatin / Q000235:genetics / Q000378:metabolism; D020868:Gene Silencing; D005800:Genes, Fungal; D006570:Heterochromatin / Q000235:genetics / Q000378:metabolism; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D056565:Sirtuin 2 / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity; D016615:Telomere / Q000235:genetics / Q000378:metabolism*
D022041:Euchromatin; D006570:Heterochromatin; D006657:Histones; C084122:SIR3 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D051548:Histone Acetyltransferases; C469266:Sas2 protein, S cerevisiae; C071665:RPD3 protein, S cerevisiae; C087778:SIR2 protein, S cerevisiae; D056565:Sirtuin 2; D006655:Histone Deacetylases