Reinventing Heterochromatin in Budding Yeasts: Sir2 and the Origin Recognition Complex Take Center Stage

Hickman, Meleah A.; Froyd, Cara A.; Rusché, Laura N.

doi:10.1128/ec.05123-11

Cited by 50 publications

(52 citation statements)

References 120 publications

(149 reference statements)

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“…S11 and S12). Most Saccharomycotina species have lost the ancestral form of eukaryotic heterochromatin, in which lysine 9 of histone H3 is methylated (27); L. starkeyi is the only Saccharomycotina species with orthologs of Schizosaccharomyces pombe Clr4 (H3K9 methyltransferase), Epe1 (H3K9 demethylase), and Swi6 (H3K9me2/3 binding chromodomain protein). We infer that mating-type switching, which requires a mechanism to silence the nonexpressed copies of MAT genes, evolved in the Saccharomycotina lineage relatively soon after the ancestral H3K9me2/3 form of heterochromatin was lost (SI Appendix, Fig.…”

Section: Resultsmentioning

confidence: 99%

Comparative genomics of biotechnologically important yeasts

Riley

Haridas

Wolfe

et al. 2016

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

313

394

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Ascomycete yeasts are metabolically diverse, with great potential for biotechnology. Here, we report the comparative genome analysis of 29 taxonomically and biotechnologically important yeasts, including 16 newly sequenced. We identify a genetic code change, CUG-Ala, in Pachysolen tannophilus in the clade sister to the known CUG-Ser clade. Our well-resolved yeast phylogeny shows that some traits, such as methylotrophy, are restricted to single clades, whereas others, such as L-rhamnose utilization, have patchy phylogenetic distributions. Gene clusters, with variable organization and distribution, encode many pathways of interest. Genomics can predict some biochemical traits precisely, but the genomic basis of others, such as xylose utilization, remains unresolved. Our data also provide insight into early evolution of ascomycetes. We document the loss of H3K9me2/3 heterochromatin, the origin of ascomycete mating-type switching, and panascomycete synteny at the MAT locus. These data and analyses will facilitate the engineering of efficient biosynthetic and degradative pathways and gateways for genomic manipulation.genomics | bioenergy | biotechnological yeasts | genetic code | microbiology Y easts are fungi that reproduce asexually by budding or fission and sexually without multicellular fruiting bodies (1, 2). Their unicellular, largely free-living lifestyle has evolved several times (3). Despite morphological similarities, yeasts constitute over 1,500 known species that inhabit many specialized environmental niches and associations, including virtually all varieties of fruits and flowers, plant surfaces and exudates, insects and other invertebrates, birds, mammals, and highly diverse soils (4). Biochemical and genomic studies of the model yeast Saccharomyces cerevisiaeessential for making bread, beer, and wine-have established much of our understanding of eukaryotic biology. However, in many ways, S. cerevisiae is an oddity among the yeasts, and many important biotechnological applications and highly divergent physiological capabilities of lesser-known yeast species have not been fully exploited (5). Various species can grow on methanol or n-alkanes as sole carbon and energy sources, overproduce vitamins and lipids, thrive under acidic conditions, and ferment unconventional carbon sources. Many features of yeasts make them ideal platforms for biotechnological processes. Their thick cell walls help them survive osmotic shock, and in contrast to bacteria, they are resistant to viruses. Their unicellular form is easy to cultivate, scale up, and harvest. The objective of this study was, therefore, to put yeasts with diverse biotechnological applications in a phylogenomic context and relate their physiologies to genomic SignificanceThe highly diverse Ascomycete yeasts have enormous biotechnological potential. Collectively, these yeasts convert a broad range of substrates into useful compounds, such as ethanol, lipids, and vitamins, and can grow in extremes of temperature, salinity, and pH. We compared 29 yeast genome...

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Section: Resultsmentioning

confidence: 99%

Comparative genomics of biotechnologically important yeasts

Riley

Haridas

Wolfe

et al. 2016

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

313

394

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“…It seems likely that the primordial system used either centromeric or telomeric heterochromatin to silence the nonexpressed MAT genes. However, all Saccharomycotina species, including H. polymorpha and P. pastoris, have lost the proteins (Clr4 and Swi6/HP1) that make the histone H3K9me modification that is characteristic of silent heterochromatin in most eukaryotes, including Schizosaccharomyces and Pezizomycotina (59). Instead, H. polymorpha may use Cse4-containing nucleosomes to silence its centromere-proximal MAT genes, similar to the mechanism proposed for neocentromeres in Candida albicans (60).…”

Section: Ab Ac Bd CD Ef Eg Fhghmentioning

confidence: 98%

Mating-type switching by chromosomal inversion in methylotrophic yeasts suggests an origin for the three-locusSaccharomyces cerevisiaesystem

Hanson

Byrne

Wolfe

2014

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

150

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Saccharomyces cerevisiae has a complex system for switching the mating type of haploid cells, requiring the genome to have three mating-type (MAT)-like loci and a mechanism for silencing two of them. How this system originated is unknown, because the threelocus system is present throughout the family Saccharomycetaceae, whereas species in the sister Candida clade have only one locus and do not switch. Here we show that yeasts in a third clade, the methylotrophs, have a simpler two-locus switching system based on reversible inversion of a section of chromosome with MATa genes at one end and MATalpha genes at the other end. In Hansenula polymorpha the 19-kb invertible region lies beside a centromere so that, depending on the orientation, either MATa or MATalpha is silenced by centromeric chromatin. In Pichia pastoris, the orientation of a 138-kb invertible region puts either MATa or MATalpha beside a telomere and represses transcription of MATa2 or MATalpha2. Both species are homothallic, and inversion of their MAT regions can be induced by crossing two strains of the same mating type. The three-locus system of S. cerevisiae, which uses a nonconservative mechanism to replace DNA at MAT, likely evolved from a conservative two-locus system that swapped genes between expression and nonexpression sites by inversion. The increasing complexity of the switching apparatus, with three loci, donor bias, and cell lineage tracking, can be explained by continuous selection to increase sporulation ability in young colonies. Our results provide an evolutionary context for the diversity of switching and silencing mechanisms.Hansenula polymorpha | Pichia pastoris | yeast genetics | comparative genomics M ating-type switching in yeasts is a highly regulated process that converts a haploid cell of one mating type into a haploid of the opposite type (1-5). Switching involves the complete deactivation of one set of regulatory genes and activation of an alternative set, but, unlike most regulatory changes, the switch is achieved by physically replacing the DNA at an expression site that is shared by both types of cell. In Saccharomyces cerevisiae the switching system uses a menagerie of molecular components (3) including three mating-type (MAT)-like loci (the expressed MAT locus and the silent loci HML and HMR); an endonuclease (HO) that creates a double-strand break at the MAT locus, which then is repaired using HMLalpha or HMRa as a donor; a mechanism (Sir1 and Sir2/3/4 proteins) for repressing transcription and HO cleavage at the silent loci; two triplicated sequences (the Z and X regions) that guide repair of the dsDNA break; a donorbias mechanism (the recombination enhancer, RE) to ensure that switching happens in the correct direction; and a cell lineagetracking mechanism (Ash1 mRNA localization) to ensure that switching occurs only in particular cells. Most of these components have no function other than facilitating switching.

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“…The study of the mechanism of silencing of these donors has occupied the attention of many labs and has provided some important insights into the way in which chromatin structure influences gene expression and recombination (see reviews by Laurenson and Rine 1992;Loo and Rine 1994;Sherman and Pillus 1997;Aström and Rine 1998;Rusche et al 2003;Hickman et al 2011). Our current understanding can be summarized as shown in Figure 4A.…”

Section: Silencing Of Hml and Hmrmentioning

confidence: 99%

Mating-Type Genes andMATSwitching inSaccharomyces cerevisiae

2012

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Mating type in Saccharomyces cerevisiae is determined by two nonhomologous alleles, MATa and MATa. These sequences encode regulators of the two different haploid mating types and of the diploids formed by their conjugation. Analysis of the MATa1, MATa1, and MATa2 alleles provided one of the earliest models of cell-type specification by transcriptional activators and repressors. Remarkably, homothallic yeast cells can switch their mating type as often as every generation by a highly choreographed, site-specific homologous recombination event that replaces one MAT allele with different DNA sequences encoding the opposite MAT allele. This replacement process involves the participation of two intact but unexpressed copies of mating-type information at the heterochromatic loci, HMLa and HMRa, which are located at opposite ends of the same chromosome-encoding MAT. The study of MAT switching has yielded important insights into the control of cell lineage, the silencing of gene expression, the formation of heterochromatin, and the regulation of accessibility of the donor sequences. Real-time analysis of MAT switching has provided the most detailed description of the molecular events that occur during the homologous recombinational repair of a programmed double-strand chromosome break. TABLE OF CONTENTS Abstract 33Introduction 34

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Reinventing Heterochromatin in Budding Yeasts: Sir2 and the Origin Recognition Complex Take Center Stage

Cited by 50 publications

References 120 publications

Comparative genomics of biotechnologically important yeasts

Comparative genomics of biotechnologically important yeasts

Mating-type switching by chromosomal inversion in methylotrophic yeasts suggests an origin for the three-locusSaccharomyces cerevisiaesystem

Mating-Type Genes andMATSwitching inSaccharomyces cerevisiae

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