Nα-acetylated Sir3 stabilizes the conformation of a nucleosome-binding loop in the BAH domain

Yang, Dongxue; Fang, Qianglin; Wang, Mingzhu; Ren, Ren; Wang, Hong; He, Min; Sun, Yao; Yang, Na; Xu, Rui-Ming

doi:10.1038/nsmb.2637

Cited by 65 publications

(49 citation statements)

References 25 publications

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“…23 Furthermore, the importance of H4-K16 for Sir3 nucleosomal recognition has been highlighted by several high-resolution structures of Sir3-nucleosome complexes. 19,24–26 These studies demonstrate that H4-K16 occupies a central cavity within the nucleosome binding domain of Sir3, consistent with previous biochemical data showing that high affinity binding of Sir3 to histone peptides 27 and to mononucleosomes is disrupted by H4-K16 acetylation or glutamine substitution. 9,28 These results contrast with several in vitro studies indicating that Sir3 has a high nonspecific binding affinity for DNA, 21,22 and that the binding of Sir3 to 6-mer nucleosomal arrays is relatively insensitive to a H4-K16Q substitution.…”

supporting

confidence: 90%

Solution-state conformation and stoichiometry of yeast Sir3 heterochromatin fibres

et al. 2014

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Heterochromatin is a repressive chromatin compartment essential for maintaining genomic integrity. A hallmark of heterochromatin is the presence of specialized nonhistone proteins that alter chromatin structure to inhibit transcription and recombination. It is generally assumed that heterochromatin is highly condensed. However, surprisingly little is known about the structure of heterochromatin or its dynamics in solution. In budding yeast, formation of heterochromatin at telomeres and the HM silent mating type loci require the Sir3 protein. Here, we use a combination of sedimentation velocity, atomic force microscopy, and nucleosomal array capture to characterize the stoichiometry and conformation of Sir3 nucleosomal arrays. The results indicate that Sir3 interacts with nucleosomal arrays with a stoichiometry of two Sir3 monomers per nucleosome. We also find that Sir3 fibers are less compact than canonical – magnesium-induced 30 nm fibers. We suggest that heterochromatin proteins promote silencing by “coating” nucleosomal arrays, stabilizing interactions between nucleosomal histones and DNA.

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confidence: 90%

Solution-state conformation and stoichiometry of yeast Sir3 heterochromatin fibres

et al. 2014

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“…Sir3 crystal structures indicate that N-terminal acetylation of this protein mediates the formation of a fine structural element that are required for function. 45,46 Notably, the mating defect associated with loss of Sir3 N-terminal acetylation can be partially suppressed by overexpression of the Hsp70 chaperone Ssb1. 20 Moreover, mutations in Sir3 that synergize with disruption of NatA to promote a more severe mating defect (E131K, T135I, L208S, S813R) 47 are predicted to alter aggregation potential and/or disorder in Sir3 (Supplementary Fig.…”

Section: Discussionmentioning

confidence: 99%

Loss of amino-terminal acetylation suppresses a prion phenotype by modulating global protein folding

et al. 2014

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N-terminal acetylation is among the most ubiquitous of protein modifications in eukaryotes. While loss of N-terminal acetylation is associated with many abnormalities, the molecular basis of these effects is known for only a few cases, where acetylation of single factors has been linked to binding avidity or metabolic stability. In contrast, the impact of N-terminal acetylation for the majority of the proteome, and its combinatorial contributions to phenotypes, are unknown. Here, by studying the yeast prion [PSI+], an amyloid of the Sup35 protein, we show that loss of N-terminal acetylation promotes general protein misfolding, a redeployment of chaperones to these substrates, and a corresponding stress response. These proteostasis changes, combined with the decreased stability of unacetylated Sup35 amyloid, reduce the size of prion aggregates and reverse their phenotypic consequences. Thus, loss of N-terminal acetylation, and its previously unanticipated role in protein biogenesis, globally resculpts the proteome to create a unique phenotype.

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“…Genetic studies suggested and biochemical studies proved that Sir3 N a acetylation increases the affinity of Sir3 for nucleosomes (Connelly et al 2006;Onishi et al 2007;van Welsem et al 2008;Sampath et al 2009). Crystallographic studies showed that the Sir3 modification stabilizes the surface of the Sir3 BAH domain at the nucleosome-binding interface (Arnaudo et al 2013;Yang et al 2013).…”

Section: Post-and Cotranslational Modification Of Sir3mentioning

confidence: 99%

The Nuts and Bolts of Transcriptionally Silent Chromatin in Saccharomyces cerevisiae

2016

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Transcriptional silencing in Saccharomyces cerevisiae occurs at several genomic sites including the silent mating-type loci, telomeres, and the ribosomal DNA (rDNA) tandem array. Epigenetic silencing at each of these domains is characterized by the absence of nearly all histone modifications, including most prominently the lack of histone H4 lysine 16 acetylation. In all cases, silencing requires Sir2, a highly-conserved NAD + -dependent histone deacetylase. At locations other than the rDNA, silencing also requires additional Sir proteins, Sir1, Sir3, and Sir4 that together form a repressive heterochromatin-like structure termed silent chromatin. The mechanisms of silent chromatin establishment, maintenance, and inheritance have been investigated extensively over the last 25 years, and these studies have revealed numerous paradigms for transcriptional repression, chromatin organization, and epigenetic gene regulation. Studies of Sir2-dependent silencing at the rDNA have also contributed to understanding the mechanisms for maintaining the stability of repetitive DNA and regulating replicative cell aging. The goal of this comprehensive review is to distill a wide array of biochemical, molecular genetic, cell biological, and genomics studies down to the "nuts and bolts" of silent chromatin and the processes that yield transcriptional silencing.

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Nα-acetylated Sir3 stabilizes the conformation of a nucleosome-binding loop in the BAH domain

Cited by 65 publications

References 25 publications

Solution-state conformation and stoichiometry of yeast Sir3 heterochromatin fibres

Solution-state conformation and stoichiometry of yeast Sir3 heterochromatin fibres

Loss of amino-terminal acetylation suppresses a prion phenotype by modulating global protein folding

The Nuts and Bolts of Transcriptionally Silent Chromatin in Saccharomyces cerevisiae

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