Cti6, a PHD Domain Protein, Bridges the Cyc8-Tup1 Corepressor and the SAGA Coactivator to Overcome Repression at GAL1

Papamichos‐Chronakis, Manolis; Petrakis, Theodoros; Ktistaki, Eleni; Topalidou, Irini; Tzamarias, Dimitris

doi:10.1016/s1097-2765(02)00545-2

Cited by 125 publications

(195 citation statements)

References 44 publications

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Section: Chromatin Immunoprecipitationmentioning

confidence: 99%

“…After reversal of cross-linking, DNA was purified by phenol-chloroform extraction and recovered by ethanol precipitation. Precipitated DNA was analyzed by molecular amplification using the 25S-1, 25S-2, 5S, and NTS primers described in Gotta et al (1997) and the POL1 primers described in Papamichos-Chronakis et al (2002).To generate the triple-HA-tagged ESA1 construct (ESA1-3HA), sequence immediately 3Ј to the ESA1 ORF was amplified using Deep-Vent polymerase (New England Biolabs) and oligos T3 and D1-ESA1 (5Ј-CGCGTTTAAACGC- A. S. Clarke et al …”

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confidence: 99%

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Distinct Roles for the Essential MYST Family HAT Esa1p in Transcriptional Silencing

Clarke

Samal

Pillus

2006

MBoC

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Among acetyltransferases, the MYST family enzyme Esa1p is distinguished for its essential function and contribution to transcriptional activation and DNA double-stranded break repair. Here we report that Esa1p also plays a key role in silencing RNA polymerase II (Pol II)-transcribed genes at telomeres and within the ribosomal DNA (rDNA) of the nucleolus. These effects are mediated through Esa1p's HAT activity and correlate with changes within the nucleolus. Esa1p is enriched within the rDNA, as is the NAD-dependent protein deacetylase Sir2p, and the acetylation levels of key Esa1p histone targets are reduced in the rDNA in esa1 mutants. Although mutants of both ESA1 and SIR2 have enhanced rates of rDNA recombination, esa1 effects are more modest yet result in distinct structural changes of rDNA chromatin. Surprisingly, increased expression of ESA1 can bypass the requirement for Sir2p in rDNA silencing, suggesting that these two enzymes with seemingly opposing activities both contribute to achieve optimal nucleolar chromatin structure and function. INTRODUCTIONHistone modifications such as phosphorylation, methylation, acetylation, and deacetylation provide a mechanism by which chromatin structure is modulated to affect gene expression both positively and negatively (for reviews see Strahl and Allis, 2000;Iizuka and Smith, 2003;Kurdistani and Grunstein, 2003). The acetylation of lysine residues on histone N-terminal tails is classically linked to increases in gene expression and more directly to roles in transcriptional activation. By contrast, deacetylation of histones is most frequently correlated with transcriptionally silent chromatin. As more is learned about the enzymes catalyzing these modifications, the histone acetyltransferases (HATs) and histone deacetylases (HDACs), simple functional distinctions between acetylation and deacetylation of histones do not hold (Iizuka and Smith, 2003). For example, in several organisms, mutations in RPD3, a gene encoding a deacetylase, lead to increases in silencing rather than the expected decreases (DeRubertis et al., 1996;Rundlett et al., 1996). This brings forward the possibility that histone acetylation may play an important part in both silent and active chromatin. In addition, coactivator proteins, such as the histone acetyltransferases p300 and CBP and nuclear hormone receptors, appear to have roles in transcriptional repression through acetylation and association with particular binding partners (for examples, see Chen and Li, 1998;Waltzer and Bienz, 1998;Baluchamy et al., 2003;Girdwood et al., 2003;Rajabi et al., 2005). Thus, understanding of multiple roles for acetylation in controlling gene expression is expanding.In Saccharomyces cerevisiae, there are three regions of the genome controlled by chromatin-mediated transcriptional silencing: telomeres, the silent mating-type loci HMR and HML, and the rDNA array. Many factors are important for transcriptional silencing at subsets of these loci including the four core histones, the repressor activator protein Rap1...

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Section: Chromatin Immunoprecipitationmentioning

confidence: 99%

mentioning

confidence: 99%

Distinct Roles for the Essential MYST Family HAT Esa1p in Transcriptional Silencing

Clarke

Samal

Pillus

2006

MBoC

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“…Molecular Biology of the Cell 4200 complex remains intact (Papamichos-Chronakis et al, 2002;Proft and Struhl, 2002;Mennella et al, 2003).…”

Section: S R Green and A D Johnsonmentioning

confidence: 99%

Promoter-dependent Roles for the Srb10 Cyclin-dependent Kinase and the Hda1 Deacetylase in Tup1-mediated Repression inSaccharomyces cerevisiae

Green

Johnson

2004

MBoC

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The Tup1-Ssn6 complex has been well characterized as a Saccharomyces cerevisiae general transcriptional repressor with functionally conserved homologues in metazoans. These homologues are essential for cell differentiation and many other developmental processes. The mechanism of repression of all of these proteins remains poorly understood. Srb10 (a cyclin-dependent kinase associated with the Mediator complex) and Hda1 (a class I histone deacetylase) have each been implicated in Tup1-mediated repression. We present a statistically based genome-wide analysis that reveals that Hda1 partially represses roughly 30% of Tup1-repressed genes, whereas Srb10 kinase activity contributes to the repression of ϳ15% of Tup1-repressed genes. These effects only partially overlap, suggesting that different Tup1-repression mechanisms predominate at different promoters. We also demonstrate a distinction between histone deacetylation and transcriptional repression. In an HDA1 deletion, many Tup1-repressed genes are hyperacetylated at lysine 18 of histone H3, yet are not derepressed, indicating deacetylation alone is not sufficient to repress most Tup1-controlled genes. In a strain lacking both Srb10 and Hda1 functions, more than half of the Tup1-repressed genes are still repressed, suggesting that Tup1-mediated repression occurs by multiple, partially overlapping mechanisms, at least one of which is unknown. INTRODUCTIONThe Tup1-Ssn6 complex is a general transcriptional repressor in Saccharomyces cerevisisae that controls a diverse set of genes generally characterized as being important for adaptation to nonstandard growth. Homologues of Tup1 have been identified in several other organisms (for example, unc-37 in Caenorhabditis elegans, Groucho in Drosophila, and TLE proteins in humans), and their repression functions are essential for embryonic development, cell differentiation, neurogenesis, and other developmental processes (Pflugrad et al., 1997;Fisher and Caudy, 1998;Levanon et al., 1998;Grbavec et al., 1999). Consequently, a better understanding of the mechanism of Tup1-mediated repression in yeast should illuminate this same process and its wide-ranging downstream consequences in other organisms. The Tup1-Ssn6 complex does not itself bind DNA but is recruited to target promoters through an association with sequence-specific DNA binding proteins; however, the crucial question of how transcriptional repression is established once this event occurs has not been clearly answered.Two models for Tup1-mediated repression are supported by a number of earlier observations. One proposes that Tup1 produces a transcriptionally repressed chromatin state by recruiting histone deacetylases (HDACs). Hda1, a class I HDAC, has emerged as the most likely deacetylase to be acting with Tup1. Hda1 binds to Tup1 in vitro and an HDA1 deletion results in hyperacetylation of histones at several Tup1-controlled genes (Wu et al., 2001). Hyperacetylation of Tup1-repressed genes also is seen when Tup1 is deleted (Bone and Roth, 2001;Davie et al., 2002). ...

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“…The washed beads were resuspended directly in 1ϫ SDS-PAGE sample buffer. All samples were separated by SDS-PAGE and autoradiographed for detection of the 35 S-labeled protein or blotted for Western analysis.…”

Section: Methodsmentioning

confidence: 99%

“…However, in the presence of osmotic stress, the Hog1 kinase phosphorylates Sko1 and converts the Sko1-Ssn6-Tup1 repressor into an activator that recruits the SAGA (SptAda-Gcn5-acetyltransferase) histone acetylase and SWI/SNF nucleosome remodeling complexes to osmotic-inducible promoters. At the GAL1 promoter, the Cti6 protein links SAGA with Ssn6-Tup1 to overcome Tup1-mediated repression, even though the corepressor remains bound to the promoter in this case (35).…”

mentioning

confidence: 99%

Physical and Functional Interaction of the Yeast Corepressor Tup1 with mRNA 5′-Triphosphatase

Mukai

Davie

Dent

2003

Journal of Biological Chemistry

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The Tup1-Ssn6 complex is an important corepressor in Saccharomyces cerevisiae that inhibits transcription through interactions with the basal transcription machinery and by remodeling chromatin. In a two-hybrid screen for factors that interact with the Schizosaccharomyces pombe Tup1 ortholog, Tup11, we isolated the pct1 ؉ cDNA. The pct1 ؉ gene encodes an mRNA 5 -triphosphatase, which catalyzes the first step of mRNA capping reactions. Pct1 did not interact with the S. pombe Ssn6 ortholog. In vitro glutathione S-transferase pull-down experiments revealed that Pct1 binds to the WD repeat regions of Tup11 and the functionally redundant Tup12 protein. Similarly, the S. cerevisiae Tup1 protein associates with the mRNA 5 -triphosphatase encoded by the CET1 gene. The highly conserved C-terminal domain of Cet1 interacts with Tup1 in vitro, and Tup1-Ssn6 complexes co-purify with the Cet1 protein, indicating that in vivo interactions also occur between these proteins. Over-expression of CET1 compromised repression of an MFA2-lacZ reporter gene that is subject to Tup1-Ssn6 repression. These genetic and biochemical interactions between Tup1-Ssn6 and Cet1 indicate that the capping enzyme associated with RNA polymerase II is a target of the corepressor complex.

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Cti6, a PHD Domain Protein, Bridges the Cyc8-Tup1 Corepressor and the SAGA Coactivator to Overcome Repression at GAL1

Cited by 125 publications

References 44 publications

Distinct Roles for the Essential MYST Family HAT Esa1p in Transcriptional Silencing

Distinct Roles for the Essential MYST Family HAT Esa1p in Transcriptional Silencing

Promoter-dependent Roles for the Srb10 Cyclin-dependent Kinase and the Hda1 Deacetylase in Tup1-mediated Repression inSaccharomyces cerevisiae

Physical and Functional Interaction of the Yeast Corepressor Tup1 with mRNA 5′-Triphosphatase

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