The Positioning and Dynamics of Origins of Replication in the Budding Yeast Nucleus

Heun, Patrick; Laroche, Thierry; Raghuraman, M. K.; Gasser, Susan M.

doi:10.1083/jcb.152.2.385

Cited by 180 publications

(173 citation statements)

References 72 publications

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“…Examples of this in yeast are the preference of telomeres (Hediger et al 2002), centromeres (Heun et al 2001a), and silenced chromatin (Maillet et al 1996;Feuerbach et al 2002) for the nuclear periphery, the localization of various highly expressed and inducible genes to nuclear pores (Brickner and Walter 2004;Casolari et al 2004Casolari et al , 2005Schmid et al 2006), and the colocalization of ribosomal DNA and a majority of tRNA genes at the nucleolus. To accommodate each of these known levels of organization, there are likely to be multiple collaborating mechanisms.…”

Section: Discussionmentioning

confidence: 99%

“…Examples include global effects like chromosome territories (Foster and Bridger 2005;Cremer et al 2006) and transcription factories (Faro-Trindade and Cook 2006), and specific effects such as telomeres and centromeres at the yeast nuclear periphery (Heun et al 2001a;Hediger et al 2002), the large ribosomal DNA repeats at the nucleoli of all organisms (Shaw et al 1995), and the 5S rDNA at or near the nucleoli of many organisms . Multiple genes alter their position when transcriptionally activated (Buchenau et al 1997;Brown et al 1999;Volpi et al 2000;Kosak et al 2002;Casolari et al 2004Casolari et al , 2005Harnicarova et al 2006), and some genes are brought together with linearly distant enhancer elements (Liu and Garrard 2005;Spilianakis et al 2005;Liu and Francke 2006;Su et al 2006).…”

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confidence: 99%

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Clustering of yeast tRNA genes is mediated by specific association of condensin with tRNA gene transcription complexes

et al. 2008

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The 274 tRNA genes in Saccharomyces cerevisiae are scattered throughout the linear maps of the 16 chromosomes, but the genes are clustered at the nucleolus when compacted in the nucleus. This clustering is dependent on intact nucleolar organization and contributes to tRNA gene-mediated (tgm) silencing of RNA polymerase II transcription near tRNA genes. After examination of the localization mechanism, we find that the chromosome-condensing complex, condensin, is involved in the clustering of tRNA genes. Conditionally defective mutations in all five subunits of condensin, which we confirm is bound to active tRNA genes in the yeast genome, lead to loss of both pol II transcriptional silencing near tRNA genes and nucleolar clustering of the genes. Furthermore, we show that condensin physically associates with a subcomplex of RNA polymerase III transcription factors on the tRNA genes. Clustering of tRNA genes by condensin appears to be a separate mechanism from their nucleolar localization, as microtubule disruption releases tRNA gene clusters from the nucleolus, but does not disperse the clusters. These observations suggest a widespread role for condensin in gene organization and packaging of the interphase yeast nucleus.[Keywords: tRNA gene; condensin; microtubules; nuclear organization; nucleolus] Supplemental material is available at http://www.genesdev.org.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Clustering of yeast tRNA genes is mediated by specific association of condensin with tRNA gene transcription complexes

et al. 2008

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“…However, the consistent localization of the IFN-c locus at the nuclear periphery even during high-level IFN-c expression in Th1 cells argues strongly that the periphery cannot be an indiscriminately repressive environment. Interestingly, telomeres and plasmids that carry late replication origins are both found at the nuclear periphery in yeast, but they do not co-localize with each other [37], suggesting that distinct 'addresses' exist within the peripheral compartment. Similarly, the molecular requirements for gene silencing within the peripheral compartment differ depending on whether loci are held in the periphery by telomeric integration (where silencing requires Ku but not nup60 or myosin-like proteins) or by tethering to the nuclear envelope (where silencing requires nup60 and myosin-like proteins) [6,[35][36][37].…”

Section: The Significance Of Locus Repositioning To Centromeric Hetermentioning

confidence: 99%

“…In the yeast Saccharomyces cerevisiae, telomeres constitute repressive chromatin domains and locate to the nuclear periphery [35]. Genes integrated in cis into yeast telomeres or tethered to the nuclear periphery independently of telomeres are subject to silencing mechanisms that require the sir family of chromatin modifiers [35][36][37].…”

Section: The Significance Of Locus Repositioning To Centromeric Hetermentioning

confidence: 99%

Nuclear repositioning marks the selective exclusion of lineage‐inappropriate transcription factor loci during T helper cell differentiation

et al. 2004

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To address how heritable patterns of gene expression are acquired during the differentiation of Th1 and Th2 cells, we analyzed the nuclear position of lineage-restricted cytokine genes and their upstream regulators by 3-dimensional fluorescence in situ hybridization. During Th1 differentiation, GATA-3 and c-maf loci, which encode upstream regulators of Th2 cytokines, were progressively repositioned to centromeric heterochromatin as defined by a c-satellite repeat probe and/or the nuclear periphery, compartments that have been associated with transcriptional repression. A third transcription factor locus, T-bet, which controls Th1-specific programs, was subject to de novo CpG methylation in a Th2 cell clone. In contrast, we did not find repositioning of the cytokine gene loci IL-2, IL-3, IL-4 or IFN-c during T helper cell differentiation. Instead, IFN-c was constitutively associated with the nuclear periphery, even when primed for expression in Th1 cells. Our results suggest that Th1/Th2 lineage commitment and differentiation involve repositioning of the regulators of cytokine expression, rather than the cytokine genes themselves.

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“…In fact, the budding yeast nucleus has a specific internal organization that is suggestive of structural elements associated with the nuclear envelope. This is highlighted by the enrichment of certain DNA sequences, such as telomeres or late firing origins of replication, at the nuclear periphery (Heun et al, 2001;Hediger and Gasser, 2002). In addition, the nucleolus is limited to a crescent-shaped region, covering about one-third of the nuclear surface (Molenaar et al, 1970;Smitt et al, 1972).…”

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Yeast Nuclear Envelope Subdomains with Distinct Abilities to Resist Membrane Expansion

Campbell

Lorenz

Witkin

et al. 2006

MBoC

117

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Little is known about what dictates the round shape of the yeast Saccharomyces cerevisiae nucleus. In spo7⌬ mutants, the nucleus is misshapen, exhibiting a single protrusion. The Spo7 protein is part of a phosphatase complex that represses phospholipid biosynthesis. Here, we report that the nuclear protrusion of spo7⌬ mutants colocalizes with the nucleolus, whereas the nuclear compartment containing the bulk of the DNA is unaffected. Using strains in which the nucleolus is not intimately associated with the nuclear envelope, we show that the single nuclear protrusion of spo7⌬ mutants is not a result of nucleolar expansion, but rather a property of the nuclear membrane. We found that in spo7⌬ mutants the peripheral endoplasmic reticulum (ER) membrane was also expanded. Because the nuclear membrane and the ER are contiguous, this finding indicates that in spo7⌬ mutants all ER membranes, with the exception of the membrane surrounding the bulk of the DNA, undergo expansion. Our results suggest that the nuclear envelope has distinct domains that differ in their ability to resist membrane expansion in response to increased phospholipid biosynthesis. We further propose that in budding yeast there is a mechanism, or structure, that restricts nuclear membrane expansion around the bulk of the DNA. INTRODUCTIONThe nucleus has a distinct organization, characterized by the presence of internal subcompartments. Moreover, in most, but not all, cell types the nucleus adopts a round shape. Understanding how this organization and shape are achieved is of major biological and medical interest. Certain cell types, such as those found in blood lineages (e.g., neutrophils, monocytes, and eosinophils), undergo dramatic nuclear shape changes as they differentiate (Gartner et al., 1990). Cancerous states are often associated with changes in nuclear morphology, most frequently nucleolar enlargement, changes in nuclear shape, or a combination of the two (Zink et al., 2004). Although these changes provide useful diagnostic markers of cancer progression, their mechanistic basis is still poorly understood. Other diseases are also associated with changes in nuclear shape and organization. For example, Hutchinson-Gilford progeria syndrome, which leads to premature aging, is caused by a specific mutation in the gene encoding A-type lamins and is associated with nuclear shape changes . Interestingly, progeria-like changes in nuclear shape are part of the normal aging process of nonneuronal cells in Caenorhabditis elegans (Haithcock et al., 2005). Genetic defects in the nuclear lamina are also associated with several types of muscular dystrophy . Nuclear lamins and their associated proteins provide both a rigid structure that helps shape the nuclear membrane and a platform onto which protein complexes and chromatin can bind (Holaska et al., 2002). Although much has been learned in recent years about the function of nuclear lamins, many significant questions remain. For example, it is not known how diseaseassociated changes in nuclear shape affect...

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The Positioning and Dynamics of Origins of Replication in the Budding Yeast Nucleus

Cited by 180 publications

References 72 publications

Clustering of yeast tRNA genes is mediated by specific association of condensin with tRNA gene transcription complexes

Clustering of yeast tRNA genes is mediated by specific association of condensin with tRNA gene transcription complexes

Nuclear repositioning marks the selective exclusion of lineage‐inappropriate transcription factor loci during T helper cell differentiation

Yeast Nuclear Envelope Subdomains with Distinct Abilities to Resist Membrane Expansion

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