Chromatin and Transcription in Yeast

Rando, Oliver J.; Winston, Fred

doi:10.1534/genetics.111.132266

Cited by 256 publications

(272 citation statements)

References 553 publications

(726 reference statements)

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“…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.…”

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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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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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“…The in vivo nucleosome eviction activity of such chromatin remodelling complexes has been shown to require histone chaperones to tether the evicted histones [7]. One of the best characterised histone chaperones is Asf1, which coordinates nucleosome dynamics at gene promoters and open reading frames [33,34].…”

Section: How Could Histone Acetylation Promote Histone Eviction?mentioning

confidence: 99%

“…The histone modifications most commonly associated with active gene transcription are histone acetylation and histone methylation [7]. Numerous enzymes have been identified that can catalyse the addition and removal of most of these modifications.…”

Section: Introductionmentioning

confidence: 99%

“…The general consensus of opinion was that promoter chromatin structure can regulate transcription by either occluding or allowing access of transcription factors to important DNA elements within the promoter to inhibit or enable transcription initiation, respectively. However, it has also been shown that during transcription elongation nucleosomes are evicted to allow passage of RNA polymerase II (Pol II), and are reassembled in its wake to maintain chromatin structure and prevent aberrant transcription initiation from occurring within transcribed genes [7]. Thus, the nucleosome dynamics required to ensure accurate gene transcription are regulated via a complex interplay between histone PTMs and non-histone proteins at both promoters and coding regions.…”

Section: Introductionmentioning

confidence: 99%

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A role for histone acetylation in regulating transcription elongation

Church

Fleming

2017

Transcription

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“…I n eukaryotic nuclei, DNA is wrapped around histones to form nucleosomes, the basic subunits of chromatin (1). The physical and chemical properties of chromatin are regulated by at least two types of enzymatic activities: chromatin remodeling and posttranslational modifications of histones and chromatin-associated proteins (2,3). These enzymatic activities directly determine the accessibility of DNA for transcription, replication, and repair.…”

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Functions for diverse metabolic activities in heterochromatin

Xue

Pillus

2016

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

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Growing evidence demonstrates that metabolism and chromatin dynamics are not separate processes but that they functionally intersect in many ways. For example, the lysine biosynthetic enzyme homocitrate synthase was recently shown to have unexpected functions in DNA damage repair, raising the question of whether other amino acid metabolic enzymes participate in chromatin regulation. Using an in silico screen combined with reporter assays, we discovered that a diverse range of metabolic enzymes function in heterochromatin regulation. Extended analysis of the glutamate dehydrogenase 1 (Gdh1) revealed that it regulates silent information regulator complex recruitment to telomeres and ribosomal DNA. Enhanced N-terminal histone H3 proteolysis is observed in GDH1 mutants, consistent with telomeric silencing defects. A conserved catalytic Asp residue is required for Gdh1's functions in telomeric silencing and H3 clipping. Genetic modulation of α-ketoglutarate levels demonstrates a key regulatory role for this metabolite in telomeric silencing. The metabolic activity of glutamate dehydrogenase thus has important and previously unsuspected roles in regulating chromatin-related processes.I n eukaryotic nuclei, DNA is wrapped around histones to form nucleosomes, the basic subunits of chromatin (1). The physical and chemical properties of chromatin are regulated by at least two types of enzymatic activities: chromatin remodeling and posttranslational modifications of histones and chromatin-associated proteins (2, 3). These enzymatic activities directly determine the accessibility of DNA for transcription, replication, and repair.In Saccharomyces cerevisiae, three genomic regions are known to contain loci repressed by chromatin-related activities. These include the HM silent mating-type loci (HMR and HML), regions within the ribosomal DNA (rDNA), and some telomeres. Transcriptional silencing at these loci is established and maintained by a number of factors, including the Sirtuin class III deacetylase activity of silent information protein 2 (Sir2). Notably, Sir2 uses NAD + as a cofactor to deacetylate histones H3 and H4 in newly deposited nucleosomes. Other than Sir2, the composition of the silencing complexes and the mechanisms of silencing are different for the three silenced regions, with the telomeres and the HM loci more similar to each other and the rDNA locus having distinct features (reviewed in ref. 4). Silencing at telomeres and the HM loci was long considered to follow a sequential model: initial deacetylation by Sir2 creates binding sites for Sir3 and Sir4, which in turn regulate the spreading of Sir2 across these regions (5). More recent high-resolution studies report a less uniform landscape for silenced chromatin (6), although the central importance of the Sir proteins remains clear. They, together with transcription factors including Rap1 and Abf1, form a multisubunit silencing complex known as the silent information regulator (SIR) complex. Silencing at the rDNA locus does not involve the SIR complex but ra...

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Chromatin and Transcription in Yeast

Cited by 256 publications

References 553 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

A role for histone acetylation in regulating transcription elongation

Functions for diverse metabolic activities in heterochromatin

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