A Histone Variant, Htz1p, and a Sir1p-like Protein, Esc2p, Mediate Silencing at HMR

Dhillon, Namrita; Kamakaka, Rohinton T.

doi:10.1016/s1097-2765(00)00076-9

Cited by 145 publications

(120 citation statements)

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“…We confirmed this nuclear localization of Gpd1p by double fluorescence microscopy co-localization of the GFP signal with Htz1p-RFP, a well characterized nuclear histone variant (Fig. 5B) (51). This shift of Gpd1p to the nucleus was common to exposure to a number of different stress conditions, including treatment with NaCl (0.3 and 0.6 M), 1 M sorbitol, 2.5 mM dithiothreitol, or 37°C heat shock (data not shown).…”

Section: Dynamic Changes In Subcellular Distribution Of Gpd1p Betweensupporting

confidence: 63%

Dynamic Changes in the Subcellular Distribution of Gpd1p in Response to Cell Stress

Jung

Marelli

Rachubinski

et al. 2010

Journal of Biological Chemistry

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Gpd1p is a cytosolic NAD؉ -dependent glycerol 3-phosphate dehydrogenase that also localizes to peroxisomes and plays an essential role in the cellular response to osmotic stress and a role in redox balance. Here, we show that Gpd1p is directed to peroxisomes by virtue of an N-terminal type 2 peroxisomal targeting signal (PTS2) in a Pex7p-dependent manner. Significantly, localization of Gpd1p to peroxisomes is dependent on the metabolic status of cells and the phosphorylation of aminoacyl residues adjacent to the targeting signal. Exposure of cells to osmotic stress induces changes in the subcellular distribution of Gpd1p to the cytosol and nucleus. This behavior is similar to Pnc1p, which is coordinately expressed with Gpd1p, and under conditions of cell stress changes its subcellular distribution from peroxisomes to the nucleus where it mediates chromatin silencing. Although peroxisomes are necessary for the ␤-oxidation of fatty acids in yeast, the localization of Gpd1p to peroxisomes is not. Rather, shifts in the distribution of Gpd1p to different cellular compartments in response to changing cellular status suggests a role for Gpd1p in the spatial regulation of redox potential, a process critical to cell survival, especially under the complex stress conditions expected to occur in the wild.Glycerol 3-phosphate dehydrogenase (Gpd1p) is one of two NAD ϩ -dependent glycerol 3-phosphate dehydrogenases in yeast (1, 2). It is classically defined as a cytosolic enzyme that catalyzes the conversion of dihydroxyacetone phosphate (DHAP) 2 and NADH to glycerol 3-phosphate (Glycerol 3-phosphate) and NAD ϩ (2). In unstressed cells, this reaction prevents the accumulation of DHAP (3), which can otherwise be transformed into methyl glyoxylate (MG) (3, 4), a toxic compound that interacts with proteins (5-7). This reaction also allows for the reoxidation of NADH to NAD ϩ , which can serve as a buffer for cytosolic redox balance, compensating for cellular reactions that produce NADH (2). Moreover, glycerol 3-phosphate is a key metabolite for the synthesis of glyceride lipids and phospholipids, as well as for the formation of glycerol (8 -12).Under hyperosmotic stress, Saccharomyces cerevisiae, as well as other yeasts, accumulates glycerol as a major solute (13,14). This increased production of glycerol is caused mainly by an enhanced activity of Gpd1p, and accordingly, Gpd1p is essential for growth under osmotic stress (2, 15). In addition, GPD1 expression is altered by a wide variety of stresses, including heat, cold, and oxidative stress (16 -18), suggesting its regulation is controlled by stress. Genome-wide monitoring of transcript changes in yeast under various stress conditions also showed that GPD1 belongs to a large group of common stressresponse genes (19, 20); however, its regulation is complex and appears to be controlled by multiple signaling pathways (21). This likely reflects the multiple metabolic changes that yeast cells undergo in response to different stresses (19,22,23) and the function of Gpd1p at the int...

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Section: Dynamic Changes In Subcellular Distribution Of Gpd1p Betweensupporting

confidence: 63%

Dynamic Changes in the Subcellular Distribution of Gpd1p in Response to Cell Stress

Jung

Marelli

Rachubinski

et al. 2010

Journal of Biological Chemistry

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“…For example, H2A.Z seems to be implicated in both the activation and repression of transcription (13,20,22,31). The reported data suggested that H2A.Z is involved in chromosome segregation (29).…”

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confidence: 88%

Weak but Uniform Enrichment of the Histone Variant macroH2A1 along the Inactive X Chromosome

Mietton

Sengupta

Molla

et al. 2009

Molecular and Cellular Biology

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We studied the enrichment and distribution of the histone variant mH2A1 in the condensed inactive X (Xi) chromosome. By using highly specific antibodies against mH2A1 and stable HEK 293 cell lines expressing either green fluorescent protein (GFP)-mH2A1 or GFP-H2A, we found that the Xi chromosome contains ϳ1.5-fold more mH2A1 than the autosomes. To determine the in vivo distribution of mH2A1 along the X chromosome, we used a native chromatin immunoprecipitation-on-chip technique. DNA isolated from mH2A1-immunoprecipitated nucleosomes from either male or female mouse liver were hybridized to tiling microarrays covering 5 kb around most promoters or the entire X chromosome. The data show that mH2A1 is uniformly distributed across the entire Xi chromosome. Interestingly, a stronger mH2A1 enrichment along the pseudoautosomal X chromosome region was observed in both sexes. Our results indicate a potential role for macroH2A in large-scale chromosome structure and genome stability.

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“…In this screen, wild-type ESC2 silences the ADE2 reporter at HMR, giving rise to red colonies, and null or partial esc2 function yields white, pink, and/or sectored colonies (Dhillon and Kamakaka 2000;Cuperus and Shore 2002). esc2 mutants were integrated into the genome at the ESC2 locus under control of the native promoter and screened for function.…”

Section: Resultsmentioning

confidence: 99%

“…Silencing assay: HMRTADE2 silencing was performed as described previously (Chi and Shore 1996;Dhillon and Kamakaka 2000). Isogenic strains were grown in YPD culture to early logarithmic phase (2-5 3 10 6 cells/ml) at 30°, and serial dilutions were plated on YPD plates to obtain welldispersed, discrete colonies.…”

Section: Methodsmentioning

confidence: 99%

“…Saccharomyces cerevisiae ESC2 (Establishment silent chromatin 2) was first identified as genes necessary for silencing at mating-type locus that, when mutated or deleted, give rise to a partial defect in gene silencing (Dhillon and Kamakaka 2000;Cuperus and Shore 2002;Andrulis et al 2004). Sequence analysis showed that Esc2 includes two tandem C-terminal SUMO-like domains and an N-terminal polar low-complexity domain, and its domain architecture is conserved in fission yeast (Rad60) and humans (NIP45) (Novatchkova et al 2005).…”

mentioning

confidence: 99%

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A SUMO-Like Domain Protein, Esc2, Is Required for Genome Integrity and Sister Chromatid Cohesion in Saccharomyces cerevisiae

et al. 2008

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The ESC2 gene encodes a protein with two tandem C-terminal SUMO-like domains and is conserved from yeasts to humans. Previous studies have implicated Esc2 in gene silencing. Here, we explore the functional significance of SUMO-like domains and describe a novel role for Esc2 in promoting genome integrity during DNA replication. This study shows that esc2D cells are modestly sensitive to hydroxyurea (HU) and defective in sister chromatid cohesion and have a reduced life span, and these effects are enhanced by deletion of the RRM3 gene that is a Pif1-like DNA helicase. esc2D rrm3D cells also have a severe growth defect and accumulate DNA damage in late S/G 2 . In contrast, esc2D does not enhance the HU sensitivity or sister chromatid cohesion defect in mrc1D cells, but rather partially suppresses both phenotypes. We also show that deletion of both Esc2 SUMO-like domains destabilizes Esc2 protein and functionally inactivates Esc2, but this phenotype is suppressed by an Esc2 variant with an authentic SUMO domain. These results suggest that Esc2 is functionally equivalent to a stable SUMO fusion protein and plays important roles in facilitating DNA replication fork progression and sister chromatid cohesion that would otherwise impede the replication fork in rrm3D cells.

show abstract

A Histone Variant, Htz1p, and a Sir1p-like Protein, Esc2p, Mediate Silencing at HMR

Cited by 145 publications

References 50 publications

Dynamic Changes in the Subcellular Distribution of Gpd1p in Response to Cell Stress

Dynamic Changes in the Subcellular Distribution of Gpd1p in Response to Cell Stress

Weak but Uniform Enrichment of the Histone Variant macroH2A1 along the Inactive X Chromosome

A SUMO-Like Domain Protein, Esc2, Is Required for Genome Integrity and Sister Chromatid Cohesion in Saccharomyces cerevisiae

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