47 results match your criteria spt3 required

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

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

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

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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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

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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A SAGA-independent function of SPT3 mediates transcriptional deregulation in a mutant of the Ccr4-not complex in Saccharomyces cerevisiae.

Genetics 2007 Sep 29;177(1):123-35. Epub 2007 Jul 29.

Department of Microbiology and Molecular Medicine, University of Geneva Medical School, Geneva 1211, Switzerland.

The conserved multi-subunit Ccr4-Not complex regulates gene expression in diverse ways. In this work, we characterize the suppression of temperature sensitivity associated with a mutation in the gene encoding the scaffold subunit of the Ccr4-Not complex, NOT1, by the deletion of SPT3. We determine that the deletion of SPT3, but not the deletion of genes encoding other subunits of the SAGA complex, globally suppresses transcriptional defects of not1-2. Read More

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September 2007

The essential gene wda encodes a WD40 repeat subunit of Drosophila SAGA required for histone H3 acetylation.

Mol Cell Biol 2006 Oct;26(19):7178-89

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

Histone acetylation provides a switch between transcriptionally repressive and permissive chromatin. By regulating the chromatin structure at specific promoters, histone acetyltransferases (HATs) carry out important functions during differentiation and development of higher eukaryotes. HAT complexes are present in organisms as diverse as Saccharomyces cerevisiae, humans, and flies. Read More

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October 2006

SWI/SNF binding to the HO promoter requires histone acetylation and stimulates TATA-binding protein recruitment.

Mol Cell Biol 2006 Jun;26(11):4095-110

Department of Pathology, University of Utah, 15 North Medical Drive East, Salt Lake City, UT 84132-2501, USA.

We use chromatin immunoprecipitation assays to show that the Gcn5 histone acetyltransferase in SAGA is required for SWI/SNF association with the HO promoter and that binding of SWI/SNF and SAGA are interdependent. Previous results showed that SWI/SNF binding to HO was Gcn5 independent, but that work used a strain with a mutation in the Ash1 daughter-specific repressor of HO expression. Here, we show that Ash1 functions as a repressor that inhibits SWI/SNF binding and that Gcn5 is required to overcome Ash1 repression in mother cells to allow HO transcription. Read More

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Both normal and polyglutamine- expanded ataxin-7 are components of TFTC-type GCN5 histone acetyltransferase- containing complexes.

Biochem Soc Symp 2006 (73):155-63

Department of Molecular Pathology, Institut de Génétique et de Biologie Moléculaire et Cellulaire, UMR 7104, CNRS/IN SER M/ULP, BP 10142, 67404 Illkirch Cedex, France.

SCA7 (spinocerebellar ataxia type 7) is a neurodegenerative disorder caused by a CAG repeat expansion in the SCA7 gene that leads to elongation of a polyglutamine tract in ataxin-7, a protein of unknown function. Sgf73, a putative yeast orthologue of ataxin-7, has been identified as a new component of the yeast SAGA (Spt/Ada/Gcn5 acetyltransferase) multisubunit complex, a co-activator required for the transcription of a subset of RNA polymerase II-dependent genes. We show here that ataxin-7 is an integral component of mammalian SAGA-like complexes, i. Read More

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Regulation of an intergenic transcript controls adjacent gene transcription in Saccharomyces cerevisiae.

Genes Dev 2005 Nov;19(22):2695-704

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

Recent studies have revealed that transcription of noncoding, intergenic DNA is abundant among eukaryotes. However, the functions of this transcription are poorly understood. We have previously shown that in Saccharomyces cerevisiae, expression of an intergenic transcript, SRG1, represses the transcription of the adjacent gene, SER3, by transcription interference. Read More

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November 2005

Interdependent recruitment of SAGA and Srb mediator by transcriptional activator Gcn4p.

Mol Cell Biol 2005 May;25(9):3461-74

Laboratory of Gene Regulation and Development, National Institute of Child Health & Human Development/NIH, Building 6A, Bethesda, MD 20892, USA.

Transcriptional activation by Gcn4p is enhanced by the coactivators SWI/SNF, SAGA, and Srb mediator, which stimulate recruitment of TATA binding protein (TBP) and polymerase II to target promoters. We show that wild-type recruitment of SAGA by Gcn4p is dependent on mediator but independent of SWI/SNF function at three different promoters. Recruitment of mediator is also independent of SWI/SNF but is enhanced by SAGA at a subset of Gcn4p target genes. Read More

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H2B ubiquitin protease Ubp8 and Sgf11 constitute a discrete functional module within the Saccharomyces cerevisiae SAGA complex.

Mol Cell Biol 2005 Feb;25(3):1162-72

The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.

The SAGA complex is a multisubunit protein complex involved in transcriptional regulation in Saccharomyces cerevisiae. SAGA combines proteins involved in interactions with DNA-bound activators and TATA-binding protein (TBP), as well as enzymes for histone acetylation (Gcn5) and histone deubiquitylation (Ubp8). We recently showed that H2B ubiquitylation and Ubp8-mediated deubiquitylation are both required for transcriptional activation. Read More

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February 2005

Positive and negative functions of the SAGA complex mediated through interaction of Spt8 with TBP and the N-terminal domain of TFIIA.

Genes Dev 2004 May;18(9):1022-34

Fred Hutchinson Cancer Research Center, and Howard Hughes Medical Institute, Seattle, WA 98109, USA.

A surface that is required for rapid formation of preinitiation complexes (PICs) was identified on the N-terminal domain (NTD) of the RNA Pol II general transcription factor TFIIA. Site-specific photocross-linkers and tethered protein cleavage reagents positioned on the NTD of TFIIA and assembled in PICs identified the SAGA subunit Spt8 and the TFIID subunit Taf4 as located near this surface. In agreement with these findings, mutations in Spt8 and the TFIIA NTD interact genetically. Read More

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Ataxin-7 is a subunit of GCN5 histone acetyltransferase-containing complexes.

Hum Mol Genet 2004 Jun 28;13(12):1257-65. Epub 2004 Apr 28.

Department of Molecular Pathology, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, Illkirch, France.

Spinocerebellar ataxia type 7 (SCA7) is a neurodegenerative disorder caused by a CAG repeat expansion in the SCA7 gene leading to elongation of a polyglutamine tract in ataxin-7, a protein of unknown function. A putative ataxin-7 yeast orthologue (SGF73) has been identified recently as a new component of the SAGA (Spt/Ada/Gcn5 acetylase) multisubunit complex, a coactivator required for transcription of a subset of RNA polymerase II-dependent genes. We show here that ataxin-7 is an integral component of the mammalian SAGA-like complexes, the TATA-binding protein-free TAF-containing complex (TFTC) and the SPT3/TAF9/GCN5 acetyltransferase complex (STAGA). Read More

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Identification, mutational analysis, and coactivator requirements of two distinct transcriptional activation domains of the Saccharomyces cerevisiae Hap4 protein.

Eukaryot Cell 2004 Apr;3(2):339-47

Graduate Program in Genetics and Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan 48824-1319, USA.

The Hap4 protein of the budding yeast Saccharomyces cerevisiae activates the transcription of genes that are required for growth on nonfermentable carbon sources. Previous reports suggested the presence of a transcriptional activation domain within the carboxyl-terminal half of Hap4 that can function in the absence of Gcn5, a transcriptional coactivator protein and histone acetyltransferase. The boundaries of this activation domain were further defined to a region encompassing amino acids 359 to 476. Read More

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Spt3 and Mot1 cooperate in nucleosome remodeling independently of TBP recruitment.

EMBO J 2004 May 1;23(9):1943-8. Epub 2004 Apr 1.

Institute of Molecular Biology and Biotechnology, FORTH, Crete, Greece.

We have investigated the requirements for nucleosome remodeling upon transcriptional induction of the GAL1 promoter. We found that remodeling was dependent on two SAGA complex components, Gcn5 and Spt3. The involvement of the latter was surprising as its function has been suggested to be directly involved in TATA-binding protein (TBP) recruitment. Read More

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Gcn4 occupancy of open reading frame regions results in the recruitment of chromatin-modifying complexes but not the mediator complex.

EMBO Rep 2003 Sep;4(9):872-6

Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology Hellas, PO Box 1527, Heraklion 711 10, Crete, Greece.

Eukaryotic transcriptional activators usually recognize short DNA motifs, which are not only located within promoter regions, but also scattered throughout the genome. Assuming that the function of activators at non-promoter regions is wasteful and perhaps harmful, one can ask whether such binding is somehow prevented or if transcription is blocked at a downstream step. Here, we show that the yeast transcriptional activator Gcn4 is associated in vivo with several non-promoter euchromatic sites. Read More

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September 2003

Differential requirement of SAGA components for recruitment of TATA-box-binding protein to promoters in vivo.

Mol Cell Biol 2002 Nov;22(21):7365-71

Howard Hughes Medical Institute, Programs in Gene Expression and Function and Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.

The multisubunit Saccharomyces cerevisiae SAGA (Spt-Ada-Gcn5-acetyltransferase) complex is required to activate transcription of a subset of RNA polymerase II-dependent genes. However, the contribution of each SAGA component to transcription activation is relatively unknown. Here, using a formaldehyde-based in vivo cross-linking and chromatin immunoprecipitation assay, we have systematically analyzed the role of SAGA components in the recruitment of TATA-box binding protein (TBP) to SAGA-dependent promoters. Read More

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November 2002

Spt3 plays opposite roles in filamentous growth in Saccharomyces cerevisiae and Candida albicans and is required for C. albicans virulence.

Genetics 2002 Jun;161(2):509-19

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

Spt3 of Saccharomyces cerevisiae is required for the normal transcription of many genes in vivo. Past studies have shown that Spt3 is required for both mating and sporulation, two events that initiate when cells are at G(1)/START. We now show that Spt3 is needed for two other events that begin at G(1)/START, diploid filamentous growth and haploid invasive growth. Read More

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Human STAGA complex is a chromatin-acetylating transcription coactivator that interacts with pre-mRNA splicing and DNA damage-binding factors in vivo.

Mol Cell Biol 2001 Oct;21(20):6782-95

Laboratories of Biochemistry and Molecular Biology, The Rockefeller University, New York, New York 10021, USA.

GCN5 is a histone acetyltransferase (HAT) originally identified in Saccharomyces cerevisiae and required for transcription of specific genes within chromatin as part of the SAGA (SPT-ADA-GCN5 acetylase) coactivator complex. Mammalian cells have two distinct GCN5 homologs (PCAF and GCN5L) that have been found in three different SAGA-like complexes (PCAF complex, TFTC [TATA-binding-protein-free TAF(II)-containing complex], and STAGA [SPT3-TAF(II)31-GCN5L acetylase]). The composition and roles of these mammalian HAT complexes are still poorly characterized. Read More

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October 2001

The S. cerevisiae SAGA complex functions in vivo as a coactivator for transcriptional activation by Gal4.

Genes Dev 2001 Aug;15(15):1946-56

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

Previous studies demonstrated that the SAGA (Spt-Ada-Gcn5-Acetyltransferase) complex facilitates the binding of TATA-binding protein (TBP) during transcriptional activation of the GAL1 gene of Saccharomyces cerevisiae. TBP binding was shown to require the SAGA components Spt3 and Spt20/Ada5, but not the SAGA component Gcn5. We have now examined whether SAGA is directly required as a coactivator in vivo by using chromatin immunoprecipitation analysis. Read More

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Inhibition of TATA-binding protein function by SAGA subunits Spt3 and Spt8 at Gcn4-activated promoters.

Mol Cell Biol 2000 Jan;20(2):634-47

The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.

SAGA is a 1.8-MDa yeast protein complex that is composed of several distinct classes of transcription-related factors, including the adaptor/acetyltransferase Gcn5, Spt proteins, and a subset of TBP-associated factors. Our results indicate that mutations that completely disrupt SAGA (deletions of SPT7 or SPT20) strongly reduce transcriptional activation at the HIS3 and TRP3 genes and that Gcn5 is required for normal HIS3 transcriptional start site selection. Read More

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January 2000

The Spt components of SAGA facilitate TBP binding to a promoter at a post-activator-binding step in vivo.

Genes Dev 1999 Nov;13(22):2940-5

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

The SAGA complex of Saccharomyces cerevisiae is required for the transcription of many RNA polymerase II-dependent genes. Previous studies have demonstrated that SAGA possesses histone acetyltransferase activity, catalyzed by the SAGA component Gcn5. However, the transcription of many genes, although SAGA dependent, is Gcn5 independent, suggesting the existence of distinct SAGA activities. Read More

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November 1999

Specific components of the SAGA complex are required for Gcn4- and Gcr1-mediated activation of the his4-912delta promoter in Saccharomyces cerevisiae.

Genetics 1999 Apr;151(4):1365-78

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

Mutations selected as suppressors of Ty or solo delta insertion mutations in Saccharomyces cerevisiae have identified several genes, SPT3, SPT7, SPT8, and SPT20, that encode components of the SAGA complex. However, the mechanism by which SAGA activates transcription of specific RNA polymerase II-dependent genes is unknown. We have conducted a fine-structure mutagenesis of one widely used SAGA-dependent promoter, the delta element of his4-912delta, to identify sequence elements important for its promoter activity. Read More

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