106 results match your criteria spt3

The function of Spt3, a subunit of the SAGA complex, in PGK1 transcription is restored only partially when reintroduced by plasmid into taf1 spt3 double mutant yeast strains.

Genes Genet Syst 2020 Aug 4;95(3):151-163. Epub 2020 Jul 4.

Molecular and Cellular Biology Laboratory, Graduate School of Medical Life Science, Yokohama City University.

In Saccharomyces cerevisiae, class II gene promoters contain two classes of TATA elements: the TATA box and the TATA-like element. Functional loss of TFIID and SAGA transcription complexes selectively impacts steady-state mRNA levels expressed from TATA-like element-containing (i.e. Read More

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Prp5-Spt8/Spt3 interaction mediates a reciprocal coupling between splicing and transcription.

Nucleic Acids Res 2020 06;48(11):5799-5813

State Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, College of Life Science, Wuhan University, Wuhan, Hubei 430072, China.

Transcription and pre-mRNA splicing are coupled to promote gene expression and regulation. However, mechanisms by which transcription and splicing influence each other are still under investigation. The ATPase Prp5p is required for pre-spliceosome assembly and splicing proofreading at the branch-point region. Read More

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Structure of the transcription coactivator SAGA.

Nature 2020 01 22;577(7792):717-720. Epub 2020 Jan 22.

Max Planck Institute for Biophysical Chemistry, Department of Molecular Biology, Göttingen, Germany.

Gene transcription by RNA polymerase II is regulated by activator proteins that recruit the coactivator complexes SAGA (Spt-Ada-Gcn5-acetyltransferase) and transcription factor IID (TFIID). SAGA is required for all regulated transcription and is conserved among eukaryotes. SAGA contains four modules: the activator-binding Tra1 module, the core module, the histone acetyltransferase (HAT) module and the histone deubiquitination (DUB) module. Read More

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January 2020

Characterization of a metazoan ADA acetyltransferase complex.

Nucleic Acids Res 2019 04;47(7):3383-3394

Stowers Institute for Medical Research, Kansas City, MO 64110, USA.

The Gcn5 acetyltransferase functions in multiple acetyltransferase complexes in yeast and metazoans. Yeast Gcn5 is part of the large SAGA (Spt-Ada-Gcn5 acetyltransferase) complex and a smaller ADA acetyltransferase complex. In flies and mammals, Gcn5 (and its homolog pCAF) is part of various versions of the SAGA complex and another large acetyltransferase complex, ATAC (Ada2A containing acetyltransferase complex). Read More

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Widespread and precise reprogramming of yeast protein-genome interactions in response to heat shock.

Genome Res 2018 Feb 14. Epub 2018 Feb 14.

Center for Eukaryotic Gene Regulation, Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, Pennsylvania 16802, USA.

Gene expression is controlled by a variety of proteins that interact with the genome. Their precise organization and mechanism of action at every promoter remains to be worked out. To better understand the physical interplay among genome-interacting proteins, we examined the temporal binding of a functionally diverse subset of these proteins: nucleosomes (H3), H2AZ (Htz1), SWR (Swr1), RSC (Rsc1, Rsc3, Rsc58, Rsc6, Rsc9, Sth1), SAGA (Spt3, Spt7, Ubp8, Sgf11), Hsf1, TFIID (Spt15/TBP and Taf1), TFIIB (Sua7), TFIIH (Ssl2), FACT (Spt16), Pol II (Rpb3), and Pol II carboxyl-terminal domain (CTD) phosphorylation at serines 2, 5, and 7. Read More

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February 2018

SAGA Is a General Cofactor for RNA Polymerase II Transcription.

Mol Cell 2017 Oct 14;68(1):130-143.e5. Epub 2017 Sep 14.

Institut de Génétique et de Biologie Moléculaire et Cellulaire, 67404 Illkirch, France; Centre National de la Recherche Scientifique, UMR7104, 67404 Illkirch, France; Institut National de la Santé et de la Recherche Médicale, U964, 67404 Illkirch, France; Université de Strasbourg, 67404 Illkirch, France. Electronic address:

Prior studies suggested that SAGA and TFIID are alternative factors that promote RNA polymerase II transcription, with about 10% of genes in S. cerevisiae dependent on SAGA. We reassessed the role of SAGA by mapping its genome-wide location and role in global transcription in budding yeast. Read More

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October 2017

Improvement of Lead Tolerance of Saccharomyces cerevisiae by Random Mutagenesis of Transcription Regulator SPT3.

Appl Biochem Biotechnol 2018 Jan 27;184(1):155-167. Epub 2017 Jun 27.

College of Food Science and Light Industry, Nanjing Tech University, Nanjing, 210009, People's Republic of China.

Bioremediation of heavy metal pollution with biomaterials such as bacteria and fungi usually suffer from limitations because of microbial sensitivity to high concentration of heavy metals. Herein, we adopted a novel random mutagenesis technique called RAISE to manipulate the transcription regulator SPT3 of Saccharomyces cerevisiae to improve cell lead tolerance. The best strain Mutant VI was selected from the random mutagenesis libraries on account of the growth performance, with higher specific growth rate than the control strain (0. Read More

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January 2018

Pharmacological characterization of synthetic serine palmitoyltransferase inhibitors by biochemical and cellular analyses.

Biochem Biophys Res Commun 2018 03 29;497(4):1171-1176. Epub 2016 Dec 29.

Biomolecular Research Laboratories, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-higashi 2-chome, Fujisawa, Kanagawa 251-8555, Japan.

Human serine palmitoyltransferase (SPT) is a PLP-dependent enzyme residing in the endoplasmic reticulum. It catalyzes the synthesis of 3-ketodihydrosphingosine (3-KDS) from the substrates palmitoyl-CoA and l-serine. It is a rate-limiting enzyme for sphingolipid synthesis in cells. Read More

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p38 MAPK mediates epithelial-mesenchymal transition by regulating p38IP and Snail in head and neck squamous cell carcinoma.

Oral Oncol 2016 09 15;60:81-9. Epub 2016 Jul 15.

Department of Head and Neck Surgery, United States; Jonsson Comprehensive Cancer Center, United States; UCLA Head and Neck Cancer Program, United States. Electronic address:

Background: In the present study, we investigated the role of p38-p38IP signaling in the inflammation-induced promotion of epithelial-to-mesenchymal transition (EMT) in Head and Neck Squamous Cell Carcinoma (HNSCC).

Methods: Quantitative RT-PCR, western blot analysis, spheroid modeling and immunohistochemical staining of human HNSCC tissue sections were used.

Results: p38 inhibitor treated and p38 shRNA HNSCC cell lines demonstrate a significant upregulation in E-cadherin mRNA and a decrease in the mRNA expression of Snail. Read More

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September 2016

SGF29 and Sry pathway in hepatocarcinogenesis.

World J Biol Chem 2015 Aug;6(3):139-47

Nobuya Kurabe, Department of Tumor Pathology, Hamamatsu University School of Medicine, Shizuoka 431-3192, Japan.

Deregulated c-Myc expression is a hallmark of many human cancers. We have recently identified a role of mammalian homolog of yeast SPT-ADA-GCN5-acetyltransferas (SAGA) complex component, SAGA-associated factor 29 (SGF29), in regulating the c-Myc overexpression. Here, we discuss the molecular nature of SFG29 in SPT3-TAF9-GCN5-acetyltransferase complex, a counterpart of yeast SAGA complex, and the mechanism through which the elevated SGF29 expression contribute to oncogenic potential of c-Myc in hepatocellularcarcinoma (HCC). Read More

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Mapping the deubiquitination module within the SAGA complex.

Structure 2014 Nov;22(11):1553-9

The molecular organization of the yeast transcriptional coactivator Spt-Ada-Gcn5 acetyltransferase (SAGA) was analyzed by single-particle electron microscopy. Complete or partial deletion of the Sgf73 subunit disconnects the deubiquitination (DUB) module from SAGA and favors in our conditions the cleavage of the C-terminal ends of the Spt7 subunit and the loss of the Spt8 subunit. The structural comparison of the wild-type SAGA with two deletion mutants positioned the DUB module and enabled the fitting of the available atomic models. Read More

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November 2014

Architecture of the Saccharomyces cerevisiae SAGA transcription coactivator complex.

EMBO J 2014 Nov 12;33(21):2534-46. Epub 2014 Sep 12.

Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

The conserved transcription coactivator SAGA is comprised of several modules that are involved in activator binding, TBP binding, histone acetylation (HAT) and deubiquitination (DUB). Crosslinking and mass spectrometry, together with genetic and biochemical analyses, were used to determine the molecular architecture of the SAGA-TBP complex. We find that the SAGA Taf and Taf-like subunits form a TFIID-like core complex at the center of SAGA that makes extensive interactions with all other SAGA modules. Read More

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November 2014

MYC interacts with the human STAGA coactivator complex via multivalent contacts with the GCN5 and TRRAP subunits.

Biochim Biophys Acta 2014 May 3;1839(5):395-405. Epub 2014 Apr 3.

Department of Biochemistry, University of California Riverside, 900 University Ave., Riverside, CA 92521, USA. Electronic address:

MYC is an oncogenic DNA-binding transcription activator of many genes and is often upregulated in human cancers. MYC has an N-terminal transcription activation domain (TAD) that is also required for cell transformation. Various MYC TAD-interacting coactivators have been identified, including the transcription/transformation-associated protein (TRRAP), a subunit of different histone acetyltransferase (HAT) complexes such as the human "SPT3-TAF9-GCN5 Acetyltransferase" (STAGA) complex involved in MYC transactivation of the TERT gene. Read More

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Transcription factors spt3 and spt8 are associated with conidiation, mycelium growth, and pathogenicity in Fusarium graminearum.

FEMS Microbiol Lett 2014 Feb 19;351(1):42-50. Epub 2013 Dec 19.

College of Plant Protection, Nanjing Agricultural University, Nanjing, China.

Fusarium graminearum (teleomorph: Gibberella zeae), the dominant pathogen of Fusarium head blight (FHB) on wheat, can cause substantial economic losses. The Spt-Ada-Gcn5-acetyltransferase (SAGA) transcription coactivator plays multiple roles in regulating transcription because of the presence of functionally independent modules of subunits within the complex. The transcription factors spt3 and spt8 are components of the SAGA complex and they are important in yeasts and filamentous fungi including F. Read More

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February 2014

SAGA complex components and acetate repression in Aspergillus nidulans.

G3 (Bethesda) 2012 Nov 1;2(11):1357-67. Epub 2012 Nov 1.

School of Molecular and Biomedical Science, University of Adelaide, Adelaide, SA 5006, Australia.

Alongside the well-established carbon catabolite repression by glucose and other sugars, acetate causes repression in Aspergillus nidulans. Mutations in creA, encoding the transcriptional repressor involved in glucose repression, also affect acetate repression, but mutations in creB or creC, encoding components of a deubiquitination system, do not. To understand the effects of acetate, we used a mutational screen that was similar to screens that uncovered mutations in creA, creB, and creC, except that glucose was replaced by acetate to identify mutations that were affected for repression by acetate but not by glucose. Read More

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November 2012

GCN5 acetylates and regulates the stability of the oncoprotein E2A-PBX1 in acute lymphoblastic leukemia.

Leukemia 2013 Mar 11;27(3):578-85. Epub 2012 Sep 11.

Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

The t(1;19) translocation in pediatric pre-B-cell acute lymphoblastic leukemia (ALL) fuses the genes, which encode the transcriptional activator E2A and homeobox pre-B-cell leukemia transcription factor 1 (PBX1), resulting in expression of the chimeric transcription factor E2A-PBX1. E2A-PBX1 can promote cell transformation both in vitro and in vivo; however, the mechanisms by which E2A-PBX1 contributes to malignancy merit further investigation. In the current work we report, for the first time, a physical and functional interaction between the SPT3-TAFII31-GCN5L acetylase (STAGA) complex and E2A-PBX1. Read More

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Increased ethanol production from glycerol by Saccharomyces cerevisiae strains with enhanced stress tolerance from the overexpression of SAGA complex components.

Enzyme Microb Technol 2012 Sep 16;51(4):237-43. Epub 2012 Jul 16.

School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.

During the industrial production of ethanol using yeast, the cells are exposed to stresses that affect their growth and productivity; therefore, stress-tolerant yeast strains are highly desirable. To increase ethanol production from glycerol, a greater tolerance to osmotic and ethanol stress was engineered in yeast strains that were impaired in endogenous glycerol production by the overexpression of both SPT3 and SPT15, components of the SAGA (Spt-Ada-Gcn5-acetyltransferase) complex. The engineered strain YPH499fps1Δgpd2Δ (pGcyaDak, pGupSpt3. Read More

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September 2012

Identification of pathogenesis-associated genes by T-DNA-mediated insertional mutagenesis in Botrytis cinerea: a type 2A phosphoprotein phosphatase and an SPT3 transcription factor have significant impact on virulence.

Mol Plant Microbe Interact 2012 Apr;25(4):481-95

Institut für Biologie und Biotechnologie der Pflanzen, Westf. Wilhelms-Universität, Hindenburgplatz 55, D-48143 Münster, Germany.

Agrobacterium tumefaciens-mediated transformation (ATMT) was used to generate an insertional mutant library of the gray mold fungus Botrytis cinerea. From a total of 2,367 transformants, 68 mutants showing significant reduction in virulence on tomato and bean plants were analyzed in detail. As reported for other fungal ATMT libraries, integrations were mostly single copy, occurred preferentially in noncoding (regulatory) regions, and were frequently accompanied by small deletions of the target sequences and loss of parts of the border sequence. Read More

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Ataxin-7 associates with microtubules and stabilizes the cytoskeletal network.

Hum Mol Genet 2012 Mar 18;21(5):1099-110. Epub 2011 Nov 18.

Department of Neuropathology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.

The spinocerebellar ataxia type 7 (SCA7) gene product, Ataxin-7 (ATXN7), localizes to the nucleus and has been shown to function as a component of the TATA-binding protein-free TAF-containing-SPT3-TAF9-GCN5-acetyltransferase transcription complex, although cytoplasmic localization of ATXN7 in affected neurons of human SCA7 patients has also been detected. Here, we define a physiological function for cytoplasmic ATXN7. Live imaging reveals that the intracellular distribution of ATXN7 dynamically changes and that ATXN7 distribution frequently shifts from the nucleus to the cytoplasm. Read More

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[Improving ethanol tolerance of Saccharomyces cerevisiae industrial strain by directed evolution of SPT3].

Sheng Wu Gong Cheng Xue Bao 2010 Feb;26(2):159-64

Department of Bioscience and Bioengineering, Dalian University of Technology, Dalian, China.

Directed evolution of transcription factors can be employed to effectively improve the phenotypes which are controlled by multiple genetic loci. In this study, we used error-prone PCR for the directed evolution of SPT3, which is the component of yeast Spt-Ada-Gcn5-acetyltransferase (SAGA) complex responsible for the transcription of stress-related genes, and studied its effect on the improvement of ethanol tolerance. Mutant library was constructed by ligating the error-prone PCR products with a modified pYES2. Read More

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February 2010

Posttranslational modification of ataxin-7 at lysine 257 prevents autophagy-mediated turnover of an N-terminal caspase-7 cleavage fragment.

J Neurosci 2009 Dec;29(48):15134-44

Buck Institute for Age Research, Novato, California 94945, USA.

Polyglutamine (polyQ) expansion within the ataxin-7 protein, a member of the STAGA [SPT3-TAF(II)31-GCN5L acetylase] and TFTC (GCN5 and TRRAP) chromatin remodeling complexes, causes the neurodegenerative disease spinocerebellar ataxia type 7 (SCA7). Proteolytic processing of ataxin-7 by caspase-7 generates N-terminal toxic polyQ-containing fragments that accumulate with disease progression and play an important role in SCA7 pathogenesis. To elucidate the basis for the toxicity of these fragments, we evaluated which posttranslational modifications of the N-terminal fragment of ataxin-7 modulate turnover and toxicity. Read More

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December 2009

Snf1p regulates Gcn5p transcriptional activity by antagonizing Spt3p.

Genetics 2010 Jan 19;184(1):91-105. Epub 2009 Oct 19.

Program in Genetics, Michigan State University, East Lansing, Michigan 48824, USA.

The budding yeast Gcn5p is a prototypic histone acetyltransferase controlling transcription of diverse genes. Here we show that Gcn5p is itself regulated by Snf1p and Spt3p. Snf1p likely controls Gcn5p via direct interaction. Read More

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January 2010

SAGA and Rpd3 chromatin modification complexes dynamically regulate heat shock gene structure and expression.

J Biol Chem 2009 Nov 15;284(47):32914-31. Epub 2009 Sep 15.

Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130-3932, USA.

The chromatin structure of heat shock protein (HSP)-encoding genes undergoes dramatic alterations upon transcriptional induction, including, in extreme cases, domain-wide nucleosome disassembly. Here, we use a combination of gene knock-out, in situ mutagenesis, chromatin immunoprecipitation, and expression assays to investigate the role of histone modification complexes in regulating heat shock gene structure and expression in Saccharomyces cerevisiae. Two histone acetyltransferases, Gcn5 and Esa1, were found to stimulate HSP gene transcription. Read More

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November 2009

Effect of overexpression of transcription factors on the fermentation properties of Saccharomyces cerevisiae industrial strains.

L Hou X Cao C Wang M Lu

Lett Appl Microbiol 2009 Jul 17;49(1):14-9. Epub 2009 Apr 17.

Key Laboratory of Food Nutrition and Safety, Ministry of Education, Tianjin University of Science and Technology, Tianjin, China.

Aims: To investigate the effect of modulation of transcription factors on the fermentation properties of Saccharomyces cerevisiae industrial strains and to evaluate whether overexpression and co-overexpression of transcription factors would result in higher ethanol yield.

Methods And Results: A mutant gene spt15 (Phe(177)Ser, Tyr(195)His, Lys(218)Arg) was constructed by polymerase chain reaction mediated site-directed mutagenesis. The fermentation properties of the engineered strains in very high gravity fermentations were investigated. Read More

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Site-specific cross-linking of TBP in vivo and in vitro reveals a direct functional interaction with the SAGA subunit Spt3.

Genes Dev 2008 Nov;22(21):2994-3006

Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.

The TATA-binding protein (TBP) is critical for transcription by all three nuclear RNA polymerases. In order to identify factors that interact with TBP, the nonnatural photoreactive amino acid rho-benzoyl-phenylalanine (BPA) was substituted onto the surface of Saccharomyces cerevisiae TBP in vivo. Cross-linking of these TBP derivatives in isolated transcription preinitiation complexes or in living cells reveals physical interactions of TBP with transcriptional coregulator subunits and with the general transcription factor TFIIA. Read More

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November 2008

Human ATAC Is a GCN5/PCAF-containing acetylase complex with a novel NC2-like histone fold module that interacts with the TATA-binding protein.

J Biol Chem 2008 Dec 6;283(49):33808-15. Epub 2008 Oct 6.

Department of Biochemistry, University of California at Riverside, CA 92521, USA.

Eukaryotic GCN5 acetyltransferases influence diverse biological processes by acetylating histones and non-histone proteins and regulating chromatin and gene-specific transcription as part of multiprotein complexes. In lower eukaryotes and invertebrates, these complexes include the yeast ADA complex that is still incompletely understood; the SAGA (Spt-Ada-Gcn5 acetylase) complexes from yeast to Drosophila that are mostly coactivators; and the ATAC (Ada Two-A containing) complex, only known in Drosophila and still poorly characterized. In contrast, vertebrate organisms, express two paralogous GCN5-like acetyltransferases (GCN5 and PCAF), which have been found so far only in SAGA-type complexes referred to hereafter as the STAGA (SPT3-TAF9-GCN5/PCAF acetylase) complexes. Read More

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December 2008

Genetic and biochemical analysis of yeast and human cap trimethylguanosine synthase: functional overlap of 2,2,7-trimethylguanosine caps, small nuclear ribonucleoprotein components, pre-mRNA splicing factors, and RNA decay pathways.

J Biol Chem 2008 Nov 5;283(46):31706-18. Epub 2008 Sep 5.

Department of Microbiology and Molecular Medicine, University of Geneva, CH1211 Geneva, Switzerland.

Trimethylguanosine synthase (Tgs1) is the enzyme that converts standard m(7)G caps to the 2,2,7-trimethylguanosine (TMG) caps characteristic of spliceosomal small nuclear RNAs. Fungi and mammalian somatic cells are able to grow in the absence of Tgs1 and TMG caps, suggesting that an essential function of the TMG cap might be obscured by functional redundancy. A systematic screen in budding yeast identified nonessential genes that, when deleted, caused synthetic growth defects with tgs1Delta. Read More

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November 2008

Characterization of new Spt3 and TATA-binding protein mutants of Saccharomyces cerevisiae: Spt3 TBP allele-specific interactions and bypass of Spt8.

Genetics 2007 Dec;177(4):2007-17

Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.

The Spt-Ada-Gcn5-acetyltransferase (SAGA) complex of Saccharomyces cerevisiae is a multifunctional coactivator complex that has been shown to regulate transcription by distinct mechanisms. Previous results have shown that the Spt3 and Spt8 components of SAGA regulate initiation of transcription of particular genes by controlling the level of TATA-binding protein (TBP/Spt15) associated with the TATA box. While biochemical evidence exists for direct Spt8-TBP interactions, similar evidence for Spt3-TBP interactions has been lacking. Read More

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December 2007

STAGA recruits Mediator to the MYC oncoprotein to stimulate transcription and cell proliferation.

Mol Cell Biol 2008 Jan 29;28(1):108-21. Epub 2007 Oct 29.

Department of Biochemistry, University of California, Riverside, Riverside, CA 92521, USA.

Activation of eukaryotic gene transcription involves the recruitment by DNA-binding activators of multiprotein histone acetyltransferase (HAT) and Mediator complexes. How these coactivator complexes functionally cooperate and the roles of the different subunits/modules remain unclear. Here we report physical interactions between the human HAT complex STAGA (SPT3-TAF9-GCN5-acetylase) and a "core" form of the Mediator complex during transcription activation by the MYC oncoprotein. Read More

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January 2008

Distinct GCN5/PCAF-containing complexes function as co-activators and are involved in transcription factor and global histone acetylation.

Z Nagy L Tora

Oncogene 2007 Aug;26(37):5341-57

Transcription Department, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS UMR7104, France.

Transcription in eukaryotes is a tightly regulated, multistep process. Gene-specific transcriptional activators, several different co-activators and general transcription factors are necessary to access specific loci to allow precise initiation of RNA polymerase II transcription. As the dense chromatin folding of the genome does not allow the access of these sites by the huge multiprotein transcription machinery, remodelling is required to loosen up the chromatin structure for successful transcription initiation. Read More

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