Control of replication initiation and heterochromatin formation in <i>Saccharomyces cerevisiae</i> by a regulator of meiotic gene expression

Irlbacher, Horst; Franke, Jacqueline; Manke, Thomas; Vingron, Martin; Ehrenhofer‐Murray, Ann E.

doi:10.1101/gad.334805

Cited by 51 publications

(60 citation statements)

References 59 publications

(86 reference statements)

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“…The binding sites for Abf1p, Rap1p, and ORC in the silencers as well as their 59 / 39 directions are indicated. In HML-E, 16 bp centromere-proximal to the ORC site is a putative Sum1p-binding site whose deletion has been shown to reduce the activity of a weakened HML-E silencer (Irlbacher et al 2005). The a1 and a2 genes at the HML locus and the a1 and a2 genes at HMR are also indicated.…”

Section: Resultsmentioning

confidence: 99%

Position Effect on the Directionality of Silencer Function in Saccharomyces cerevisiae

Zou

Chiu³

et al. 2006

Genetics

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In Saccharomyces cerevisiae, silencers flanking the HML and HMR loci initiate the establishment of transcriptional silencing. We demonstrate that the activity of a silencer pertaining to its potency and directionality is dependent on its genomic position. The context of the HML-E silencer is more permissive to silencer function than that of HML-I or HMR-E, despite that HML-E and HML-I are only 3.3 kb apart. The apparent strength and directionality of a silencer in a particular location is affected by other silencing elements (silencers and protosilencers) present in its context. We show that at the HML locus, at least four silencing elements engage in multiple functional interactions that contribute to the activities of the silencers. Notably, these dispersed silencing elements can synergize to silence genes located not only inside, but also outside the HML sequence that harbors them. Moreover, the relative positions and orientations of these elements are important for silencing, indicating that they belong to an intricate silencing network.

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Section: Resultsmentioning

confidence: 99%

Position Effect on the Directionality of Silencer Function in Saccharomyces cerevisiae

Zou

Chiu³

et al. 2006

Genetics

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“…Spreading is in many ways analogous to the behavior of the Sir2/3/4 complex (e.g., H4K16 is deacetylated) yet in other ways distinct (e.g., unstable and nonheritable repression) (Rusche and Rine 2001;Sutton et al 2001;Lynch et al 2005;Valenzuela et al 2006;Prescott et al 2011). In this context, it should also be mentioned that Sum1 normally associates with the HML-E silencer at a 10-bp site called D2, where it is required for silencing under weakened conditions (see Figure 3; Irlbacher et al 2005). Hst1 is not required for HML silencing.…”

Section: The Functional Silencing Relationship Between Sir2 and Its Pmentioning

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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“…In contrast, genes involved in telomere maintenance and localization (HDF1, HDF2, MRE11, XRS2, and RAD50) Fisher and Zakian, 2005;Mueller et al, 2006). Finally, the histone methylase COMPASS (Mueller et al, 2006), the histone acetyl transferase NuA4 (Babiarz et al, 2006;Clarke et al, 2006), the histone chaperone CAF-1 (Mueller et al, 2006;Tamburini et al, 2006), cohesin (Suter et al, 2004Chang et al, 2005), SUM1 (Irlbacher et al, 2005), and SCP160 (Marsellach et al, 2006) were also implicated in telomeric silencing. There is a puzzling link between DNA replication and silencing.…”

mentioning

confidence: 99%

SubtelomericACS-containing Proto-silencers Act as Antisilencers in Replication Factors Mutants inSaccharomyces cerevisiae

Rehman

Wang

Fourel

et al. 2009

MBoC

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Subtelomeric genes are either fully active or completely repressed and can switch their state about once per 20 generations. This meta-stable telomeric position effect is mediated by strong repression signals emitted by the telomere and relayed/enhanced by weaker repressor elements called proto-silencers. In addition, subtelomeric regions contain sequences with chromatin partitioning and antisilencing activities referred to as subtelomeric antisilencing regions. Using extensive mutational analysis of subtelomeric elements, we show that ARS consensus sequence (ACS)-containing protosilencers convert to antisilencers in several replication factor mutants. We point out the significance of the B1 auxiliary sequence next to ACS in mediating these effects. In contrast, an origin-derived ACS does not convert to antisilencer in mutants and its B1 element has little bearing on silencing. These results are specific for the analyzed ACS and in addition to the effects of each mutation (relative to wild type) on global silencing. Another line of experiments shows that Mcm5p possesses antisilencing activity and is recruited to telomeres in an ACS-dependent manner. Mcm5p persists at this location at the late stages of S phase. We propose that telomeric ACS are not static proto-silencers but conduct finely tuned silencing and antisilencing activities mediated by ACS-bound factors. INTRODUCTIONGenes positioned close to telomeres are either fully active or completely repressed. They switch their state of expression once per 20 generations on average. This meta-stable telomeric position effect (TPE) is governed by strong repression signals emitted by the telomeres (Fourel et al., 2002a;Tham and Zakian, 2002;Rusche et al., 2003). Weaker repressor elements in the core X-and YЈ-subtelomeric elements, called proto-silencers, can relay and enhance repression signals away from telomeres (Fourel et al., 2002a). To date, protosilencer activity has been demonstrated for ARS consensus sites (ACS) and for the binding sites for Rap1p and Abf1p (Boscheron et al., 1996;Fourel et al., 1999;Pryde and Louis, 1999;Lebrun et al., 2001). In addition, subtelomeric core X-and YЈ-elements contain sequences, which display chromatin partitioning or antisilencing activities and are referred to as subtelomeric antisilencing regions (STARS) (Fourel et al., 1999(Fourel et al., , 2004Pryde and Louis, 1999). The state of gene expression at individual telomeres is determined by the complex interplay between the telomere, proto-silencers, and antisilencers (Fourel et al., 1999;Pryde and Louis, 1999;Lebrun et al., 2001;Fourel et al., 2002aFourel et al., , 2004Rehman et al., 2006); however, it is not clear whether and how these elements contribute to the variegated nature of TPE.ACS is a conserved 11-base pair sequence found in all yeast origins of replication, in subtelomeric core X-and YЈ-elements and in the silencers of the mating type loci. ACS binds origin recognition complex (ORC) and is essential for replication initiation at origins and for silencing at the...

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Control of replication initiation and heterochromatin formation in Saccharomyces cerevisiae by a regulator of meiotic gene expression

Cited by 51 publications

References 59 publications

Position Effect on the Directionality of Silencer Function in Saccharomyces cerevisiae

Position Effect on the Directionality of Silencer Function in Saccharomyces cerevisiae

The Nuts and Bolts of Transcriptionally Silent Chromatin in Saccharomyces cerevisiae

SubtelomericACS-containing Proto-silencers Act as Antisilencers in Replication Factors Mutants inSaccharomyces cerevisiae

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