Transcriptional silencing in yeast is associated with reduced nucleosome acetylation.

Abstract

Two classes of sequences in the yeast Saccharomyces cerevisiae are subject to transcriptional silencing: the silent mating-type cassettes and telomeres. In this report we demonstrate that the silencing of these regions is strictly associated with acetylation of the e-amino groups of lysines in the amino-terminal domains of three of the four core histones. Both the silent mating-type cassettes and the Y domains of telomeres are packaged in nucleosomes in vivo that are hypoacetylated relative to those packaging active genes. This difference in acetylation is eliminated by genetic inactivation of silencing: The silent cassettes from sir2, sir3, or sir4 cells show the same level of acetylation as other active genes. The correspondence of silencing and hypoacetylation of the mating-type cassettes is observed even for an allele lacking a promoter, indicating that silencing per se, rather than the absence of transcription, is correlated with hypoacetylation. Finally, overexpression of Sir2p, a protein required for transcriptional silencing in yeast, yields substantial histone deacetylation in vivo. These studies fortify the hypothesis that silencing in yeast results from heterochromatin formation and argue that the silencing proteins participate in this formation.

Gene induction in response to unfolded protein in the endoplasmic reticulum is mediated through Ire1p kinase interaction with a transcriptional coactivator complex containing Ada5p

“…Acetylation of histones is a landmark of transcriptionally active chromatin (30), whereas deacetylation of histones correlates with transcriptional silencing (31). The amount of histone acetylation is determined by an equilibrium between acetylase and deacetylase activities, suggesting that chromatin structure could be reversibly modified by targeting histone acetylase and deacetylase to a specific gene.…”

NAD+-dependent deacetylation of H4 lysine 16 by class III HDACs

“…Sir2-compacted chromatin is characterized by hypoacetylation of lysine residues in the N-terminal tails of histones H3 and H4 (Braunstein et al, 1993), and a very distinctive mark, hypoacetylation of H4K16 that is a signature of Sir2 silencing (Guarente, 1999;Suka et al, 2001;Robyr et al, 2002). Of all the Sir proteins (Sir1-4p), Sir2p is the only one required for the silencing of the three loci, suggesting that Sir2p is a major activity in the process.…”

SIRT1 deacetylase in aging‐induced neuromuscular degeneration and amyotrophic lateral sclerosis

“…SIRT1 is a nicotinamide adenine dinucleotide (NAD+)‐dependent deacetylase that catalyzes the removal of acetyl groups from lysine residues on histone proteins, resulting in gene silencing (Braunstein, Rose, Holmes, Allis, & Broach, 1993; Imai, Armstrong, Kaeberlein, & Guarente, 2000; Tanny, Dowd, Huang, Hilz, & Moazed, 1999). SIRT1 also deacetylates transcription factors including PGC1α, which induces mitochondrial oxidative phosphorylation (Lagouge et al, 2006), p53, which promotes cell survival (Luo et al, 2001; Vaziri et al, 2001) and triggers adaptation to calorie restriction with its accompanying stress resistance (Guarente, 2013).…”