Persistence of an alternate chromatin structure at silenced loci in the absence of silencers

Cheng, Tzu Hao; Li, Yao Cheng; Gartenberg, Marc R.

doi:10.1073/pnas.95.10.5521

Cited by 57 publications

(57 citation statements)

References 44 publications

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“…However, the notion of a silent chromatin-mediated fold back was supported by the use of novel, transcriptional-reporter constructs that detected long-range interactions within silenced subtelomeric regions (de Bruin et al 2001). Later studies suggested that the HM loci also fold back upon themselves, consistent with earlier findings that the DNA supercoiling of the silenced domains was altered (Bi and Broach 1997;Cheng et al 1998;Valenzuela et al 2008). Molecular genetic studies showed that distant silencers synergize one another, as if they interact physically Fourel et al 1999;Pryde and Louis 1999;Cheng and Gartenberg 2000;Oki et al 2004;Valenzuela et al 2008).…”

Section: Higher-order Structures Within Silenced Chromosomal Domainssupporting

confidence: 58%

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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Section: Higher-order Structures Within Silenced Chromosomal Domainssupporting

confidence: 58%

The Nuts and Bolts of Transcriptionally Silent Chromatin in Saccharomyces cerevisiae

2016

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“…In this scenario, ADE2 activation would occur following a cell cycle event, such as DNA replication, that compromises silencing efficiency (4). Silent chromatin would persist on both sides of the activated domain because the silencers stabilized the existing repressed state (2,13,14,42,50). However, it is hard to visualize how this mechanism lends itself to stable inheritance (which we observe in our assays).…”

Section: Discussionmentioning

confidence: 99%

Long-Range Communication between the Silencers of HMR

Valenzuela

Dhillon

Dubey

et al. 2008

Molecular and Cellular Biology

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Gene regulation involves long-range communication between silencers, enhancers, and promoters. In Saccharomyces cerevisiae, silencers flank transcriptionally repressed genes to mediate regional silencing. Silencers recruit the Sir proteins, which then spread along chromatin to encompass the entire silenced domain. In this report we have employed a boundary trap assay, an enhancer activity assay, chromatin immunoprecipitations, and chromosome conformation capture analyses to demonstrate that the two HMR silencer elements are in close proximity and functionally communicate with one another in vivo. We further show that silencing is necessary for these long-range interactions, and we present models for Sir-mediated silencing based upon these results.Gene activation and gene repression are central to the proper development and differentiation of organisms. DNA elements such as promoters, enhancers, and silencers play a central role in eukaryotic gene regulation. These elements are separated from each other by several kilobase pairs of DNA but are able to communicate with one another to regulate the activation or repression of genes. The exact mechanism by which distally located elements communicate with one another is not clear and is one of the key questions in gene regulation. Long-range communication between distantly located elements in chromosomes is thought to occur by one of two principal mechanisms (8). One class of models postulate that a signal emanating from a distal regulatory element spreads along the DNA fiber until it encounters a proximal regulatory element. A second class of models postulate that distal and proximal regulatory elements interact with one another directly, with the intervening DNA forming a loop. Both mechanisms must function within the context of the global chromosome structure, which appears to be composed of large chromosome loops that attach to a proteinaceous superstructure (11). The nucleus appears to be divided further into distinct chromatin compartments, with heterochromatic domains being present in regions near the nuclear periphery while euchromatic domains are found mainly in the interior of the nucleus, although a significant portion of euchromatin is located near nuclear pores.It has been suggested that the functionally and structurally defined chromatin domains may be coincident (36). Enhancers and locus control regions (LCRs) are long-range regulatory elements that activate promoters in a distance-and orientation-independent manner, and recent studies indicate that enhancers and LCRs often cluster together in three-dimensional space to form an "active chromatin hub" (23,49,58,59).Similarly, in yeast the promoters and terminators of genes are in close proximity to one another (3, 48) and tethered to the nuclear pore (10, 52). The consequence of this spatial organization is that the DNA between these regulatory elements is looped out. It is thought that the formation of these nuclear substructures aids in transcription activation.Silencers are negative regulatory element...

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“…Repression of histone gene transcription leads to a loss of nucleosomes, detected by altered DNA linking number, and to alterations in transcriptional regulation (Han et al, 1987). Mutations in the SIR regulatory genes, in addition to causing a loss of silencing at the silent mating type loci, lead to a change in the linking number of plasmids containing silent mating type loci (Abraham et al, 1983;Bi and Broach, 1997;Cheng et al, 1998). Figure 7 shows the results of an experiment designed to measure linking numbers of circular DNAs.…”

Section: Mutations In Act3 Affect Chromatin Structurementioning

confidence: 99%

The Nuclear Actin-related Protein ofSaccharomyces cerevisiae, Act3p/Arp4, Interacts with Core Histones

Harata

Oma

Mizuno

et al. 1999

MBoC

119

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Act3p/Arp4, an essential actin-related protein of Saccharomyces cerevisiae located within the nucleus, is, according to genetic data, involved in transcriptional regulation. In addition to the basal core structure of the actin family members, which is responsible for ATPase activity, Act3p possesses two insertions, insertions I and II, the latter of which is predicted to form a loop-like structure protruding from beyond the surface of the molecule. Because Act3p is a constituent of chromatin but itself does not bind to DNA, we hypothesized that insertion II might be responsible for an Act3p-specific function through its interaction with some other chromatin protein. Far Western blot and two-hybrid analyses revealed the ability of insertion II to bind to each of the core histones, although with somewhat different affinities. Together with our finding of coimmunoprecipitation of Act3p with histone H2A, this suggests the in vivo existence of a protein complex required for correct expression of particular genes. We also show that a conditional act3 mutation affects chromatin structure of an episomal DNA molecule, indicating that the putative Act3p complex may be involved in the establishment, remodeling, or maintenance of chromatin structures.

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Persistence of an alternate chromatin structure at silenced loci in the absence of silencers

Cited by 57 publications

References 44 publications

The Nuts and Bolts of Transcriptionally Silent Chromatin in Saccharomyces cerevisiae

The Nuts and Bolts of Transcriptionally Silent Chromatin in Saccharomyces cerevisiae

Long-Range Communication between the Silencers of HMR

The Nuclear Actin-related Protein ofSaccharomyces cerevisiae, Act3p/Arp4, Interacts with Core Histones

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