Tight protein–DNA interactions favor gene silencing

Dubarry, Marion; Loïodice, Isabelle; Chen, Chun-Long; Thermes, Claude; Taddei, Angela

doi:10.1101/gad.611011

Cited by 75 publications

(97 citation statements)

References 36 publications

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“…One simple model posits that SWI/SNF is required for efficient replication through SIR heterochromatin and that HU-induced fork stress heightens the need for SWI/SNF to remove Sir3p. Alternatively, Taddei and colleagues have shown that Sir proteins can be recruited to stalled replication forks (34). Perhaps SWI/SNF plays a role in removing Sir proteins from stalled forks, alleviating the negative consequences of this Sir recruitment.…”

Section: Discussionmentioning

confidence: 99%

Direct interactions promote eviction of the Sir3 heterochromatin protein by the SWI/SNF chromatin remodeling enzyme

Manning

Peterson

2014

Proc. Natl. Acad. Sci. U.S.A.

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Heterochromatin is a specialized chromatin structure that is central to eukaryotic transcriptional regulation and genome stability. Despite its globally repressive role, heterochromatin must also be dynamic, allowing for its repair and replication. In budding yeast, heterochromatin formation requires silent information regulators (Sirs) Sir2p, Sir3p, and Sir4p, and these Sir proteins create specialized chromatin structures at telomeres and silent mating-type loci. Previously, we found that the SWI/SNF chromatin remodeling enzyme can catalyze the ATP-dependent eviction of Sir3p from recombinant nucleosomal arrays, and this activity enhances early steps of recombinational repair in vitro. Here, we show that the ATPase subunit of SWI/SNF, Swi2p/Snf2p, interacts with the heterochromatin structural protein Sir3p. Two interaction surfaces are defined, including an interaction between the ATPase domain of Swi2p and the nucleosome binding, Bromo-AdjacentHomology domain of Sir3p. A SWI/SNF complex harboring a Swi2p subunit that lacks this Sir3p interaction surface is unable to evict Sir3p from nucleosomes, even though its ATPase and remodeling activities are intact. In addition, we find that the interaction between Swi2p and Sir3p is key for SWI/SNF to promote resistance to replication stress in vivo and for establishment of heterochromatin at telomeres.A ll eukaryotic genomes are stored within the nucleoprotein structure of chromatin, the core subunit of which, the nucleosome, consists of 147 base pairs (bp) of DNA wrapped ∼1.7 times around an octamer of histone proteins (1). Over millions of years, eukaryotes have incorporated chromatin structure into the regulation of many aspects of DNA metabolism, from simple nuclear packaging to transcriptional control (2). This diversity of purpose is reflected in two general types of chromatin structures within the nucleus-euchromatin, which is decondensed and transcriptionally active, and heterochromatin, which is typically localized to the nuclear periphery and repressive for DNA recombination and transcription. Heterochromatin structures are commonly associated with centromeres and telomeres, and these domains package much of a genome's repetitive DNA (3). Consequently, the maintenance of heterochromatin is key for genomic integrity, because it prevents illicit recombination among DNA repeats and promotes chromosome segregation during mitosis (4, 5).On a molecular level, heterochromatic loci are marked by specific chromatin posttranslational modifications, which are recognized and bound by characteristic nonhistone proteins. In many vertebrates, heterochromatin is characterized by members of the heterochromatin protein 1 (HP1) family of proteins, whereas in budding yeast, the silent information regulator (Sir) proteins, Sir2p, Sir3p, and Sir4p, create heterochromatin structures at telomeres and the silent mating-type loci (6, 7). Sir3p is believed to be the key structural component of yeast heterochromatin-Sir3p contains numerous protein-protein interaction motifs (8-10), incl...

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Section: Discussionmentioning

confidence: 99%

Direct interactions promote eviction of the Sir3 heterochromatin protein by the SWI/SNF chromatin remodeling enzyme

Manning

Peterson

2014

Proc. Natl. Acad. Sci. U.S.A.

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“…Intriguingly, tight protein-DNA interactions, like those formed by the Pol III machinery at tRNA genes, promote recruitment of Sir2/3/4 complexes to chromatin in certain contexts (Dubarry et al 2011). Typically, this activity is suppressed by the Rrm3 helicase that facilitates replication-fork passage through nonhistone DNA complexes.…”

Section: Potential Cell Cycle Regulators Of Silent Chromatin Establismentioning

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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“…This, in combination, with the expression of a green fluorescent protein (GFP)-LacI repressor allows for visualization of promoter location in the embryo and throughout larval stages in development. Importantly, for tracking genes with the LacO repeats inserted, small arrays are used so as to not introduce potential chromatin structure artifacts (e.g., the array acting as a silencer itself) (44), and results are further validated by fluorescence in situ hybridization (FISH). With the LacO system, both gut (pha-4)-and muscle (myo-3)-specific promoters are inactive and sequestered at the nuclear periphery throughout early development; however, the promoters are transcriptionally active and found in the nuclear interior in differentiated gut and muscle cells, respectively (45).…”

Section: Gene Positioning To the C Elegans Npcmentioning

confidence: 99%

From Hypothesis to Mechanism: Uncovering Nuclear Pore Complex Links to Gene Expression

Burns

Wente

2014

Molecular and Cellular Biology

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The gene gating hypothesis put forth by Blobel in 1985 was an alluring proposal outlining functions for the nuclear pore complex (NPC) in transcription and nuclear architecture. Over the past several decades, collective studies have unveiled a full catalog of nucleoporins (Nups) that comprise the NPC, structural arrangements of Nups in the nuclear pore, and mechanisms of nucleocytoplasmic transport. With this foundation, investigations of the gene gating hypothesis have now become possible. Studies of several model organisms provide credence for Nup functions in transcription, mRNA export, and genome organization. Surprisingly, Nups are not only involved in transcriptional events that occur at the nuclear periphery, but there are also novel roles for dynamic Nups within the nucleoplasmic compartment. Several tenants of the original gene gating hypothesis have yet to be addressed. Knowledge of whether the NPC impacts the organization of the genome to control subsets of genes is limited, and the cooperating molecular machinery or specific genomic anchoring sequences are not fully resolved. This minireview summarizes the current evidence for gene gating in Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, and mammalian model systems. These examples highlight new and unpredicted mechanisms for Nup impacts on transcription and questions that are left to be explored.

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Tight protein–DNA interactions favor gene silencing

Cited by 75 publications

References 36 publications

Direct interactions promote eviction of the Sir3 heterochromatin protein by the SWI/SNF chromatin remodeling enzyme

Direct interactions promote eviction of the Sir3 heterochromatin protein by the SWI/SNF chromatin remodeling enzyme

The Nuts and Bolts of Transcriptionally Silent Chromatin in Saccharomyces cerevisiae

From Hypothesis to Mechanism: Uncovering Nuclear Pore Complex Links to Gene Expression

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