Sir2p and Sas2p opposingly regulate acetylation of yeast histone H4 lysine16 and spreading of heterochromatin.
The Sir3 protein helps form telomeric heterochromatin by interacting with hypoacetylated histone H4 lysine 16 (H4-Lys16). The molecular nature of the heterochromatin boundary is still unknown. Here we show that the MYST-like acetyltransferase Sas2p is required for the acetylation (Ac) of H4-Lys16 in euchromatin. In a sas2Delta strain or a phenocopy Lys16Arg mutant, Sir3p spreads from roughly 3 kb to roughly 15 kb, causing hypoacetylation and repression of adjacent chromatin. We also found that disruption of Sir3p binding in a deacetylase-deficient Sir 2Delta strain can be suppressed by sas2Delta. These data indicate that opposing effects of Sir2p and Sas2p on acetylation of H4-Lys16 maintain the boundary at telomeric heterochromatin.
Suka
Noriyuki
N
Department of Biological Chemistry, UCLA School of Medicine and the Molecular Biology Institute, Boyer Hall, University of California, Los Angeles, California 90095, USA.
Luo
Kunheng
K
Grunstein
Michael
M
D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism / Q000502:physiology*; D001120:Arginine; D002843:Chromatin / Q000378:metabolism; D006570:Heterochromatin / Q000737:chemistry / Q000378:metabolism*; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases / Q000378:metabolism / Q000502:physiology*; D006657:Histones / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism*; D009154:Mutation; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism / Q000502:physiology*; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000378:metabolism / Q000502:physiology*; D056565:Sirtuin 2; D037761:Sirtuins / Q000378:metabolism / Q000502:physiology*; D016615:Telomere / Q000648:ultrastructure
D002843:Chromatin; D006570:Heterochromatin; D006657:Histones; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D001120:Arginine; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; C469266:Sas2 protein, S cerevisiae; C087778:SIR2 protein, S cerevisiae; D056565:Sirtuin 2; D037761:Sirtuins; D006655:Histone Deacetylases; D008239:Lysine