The silencing complex SAS-I links histone acetylation to the assembly of repressed chromatin by CAF-I and Asf1 in Saccharomyces cerevisiae

Abstract

The acetylation state of histones plays a central role in determining gene expression in chromatin. The reestablishment of the acetylation state of nucleosomes after DNA replication and chromatin assembly requires both deacetylation and acetylation of specific lysine residues on newly incorporated histones. In this study, the MYST family acetyltransferase Sas2 was found to interact with Cac1, the largest subunit of Saccharomyces cerevisiae chromatin assembly factor-I (CAF-I), and with the nucleosome assembly factor Asf1. The deletions of CAC1 (cac1⌬), ASF1 (asf1⌬), and SAS2 (sas2⌬) had similar effects on gene silencing and were partially overlapping. Furthermore, Sas2 was found in a nuclear protein complex that included Sas4 and Sas5, a homolog of TAF II 30. This complex, termed SAS-I, was also found to contribute to rDNA silencing. Furthermore, the observation that a mutation of H4 lysine 16 to arginine displayed the identical silencing phenotypes as sas2⌬ suggested that it was the in vivo target of Sas2 acetylation. In summary, our data present a novel model for the reestablishment of acetylation patterns after DNA replication, by which SAS-I is recruited to freshly replicated DNA by its association with chromatin assembly complexes to acetylate lysine 16 of H4.

Rpd3-dependent boundary formation at telomeres by removal of Sir2 substrate

“…Contrary to this assumption, H4 K16R mutations cause a strong loss of telomeric silencing and defects in HM silencing ( Fig. S2) (26,30), showing that the K16R mutation is not equivalent to a deacetylated lysine. We propose that H4 K16R suppresses the sas2Δ rpd3Δ lethality through its derepressing effect on telomeric silencing.…”

“…The SAS-I complex globally acetylates H4 K16 (26,27). To search for factors that become essential in the absence of Sas2, we performed a synthetic lethal screen with sas2Δ cells.…”

Widespread regulation of gene expression in the Drosophila genome by the histone acetyltransferase dTip60

“…Notably, one homolog of dTip60, Sas2 in S. cerevisiae, has also been implicated in gene silencing at yeast telomeres and the silent mating-type loci (Ehrenhofer-Murray et al, 1997;Meijsing and Ehrenhofer-Murray, 2001;Reifsnyder et al, 1996). However, Sas2's telomeric silencing function stems from its role as a boundary factor in preventing the spreading of heterochromatin into euchromatic regions (Kimura et al, 2002;Suka et al, 2002), rather than from direct promoter acetylation.…”

The eleven-nineteen-leukemia protein ENL connects nuclear MLL fusion partners with chromatin

“…YEATS domain proteins seem to play a key role in the network of nuclear MLL fusion partners. In S. cerevisiae, this protein family is involved in histone modification (Cairns et al, 1996;Meijsing and Ehrenhofer-Murray, 2001;Le Masson et al, 2003;Sutton et al, 2003;Bittner et al, 2004;Zhang et al, 2004). The histone binding capability of the ENL YEATS motif supports a similar function for the mammalian counterparts.…”