Mutations that suppress the deletion of an upstream activating sequence in yeast: involvement of a protein kinase and histone H3 in repressing transcription in vivo.

Regulated transcription of most protein-encoding genes in Saccharomyces cerevisiae requires an upstream activating sequence (UAS); in the absence of UAS elements, little or no transcription occurs. In certain mutant strains, however, promoters that have been deleted for their UAS can direct significant levels of transcription, indicating that the remaining promoter elements (the basal promoter) are capable of directing higher levels of transcription, but they are normally represented in wild-type strains. To analyze this repression, we have selected for mutations that cause increased transcription of the SUC2 gene in the absence of its UAS. In addition to some previously studied genes, this selection has identified five genes that we have designated BUR1, BUR2, BUR3, BUR5 and BUR6 (for Bypass UAS Requirement). The bur mutations cause pleiotropic phenotypes, indicating that they affect transcription of many genes. Furthermore, some bur mutations suppress the requirement for the SNF5 trans-activator at both SUC2 and Ty. Additional analysis has demonstrated that BUR1 is identical to SGV1, which encodes a CDC28-related protein kinase. This result indicates that protein phosphorylation is important for repression of the SUC2 basal promoter as well as other aspects of transcription in vivo. Finally, BUR5 is identical to HHT1, encoding histone H3, further implicating chromatin structure as important for expression of SUC2.

[1]  J. Workman,et al.  Nucleosome core displacement in vitro via a metastable transcription factor-nucleosome complex. , 1992, Science.

[2]  F. Winston,et al.  Yeast SNF/SWI transcriptional activators and the SPT/SIN chromatin connection. , 1992, Trends in genetics : TIG.

[3]  F. Winston,et al.  SPT4, SPT5 and SPT6 interactions: effects on transcription and viability in Saccharomyces cerevisiae. , 1992, Genetics.

[4]  D. Stillman,et al.  Involvement of the SIN4 global transcriptional regulator in the chromatin structure of Saccharomyces cerevisiae , 1992, Molecular and cellular biology.

[5]  M. Carlson,et al.  Yeast SNF2/SWI2, SNF5, and SNF6 proteins function coordinately with the gene-specific transcriptional activators GAL4 and Bicoid. , 1992, Genes & development.

[6]  D. Reinberg,et al.  Human general transcription factor IIH phosphorylates the C-terminal domain of RNA polymerase II , 1992, Nature.

[7]  D. Reinberg,et al.  Dr1, a TATA-binding protein-associated phosphoprotein and inhibitor of class II gene transcription , 1992, Cell.

[8]  J. Thorner,et al.  A presumptive helicase (MOT1 gene product) affects gene expression and is required for viability in the yeast Saccharomyces cerevisiae , 1992, Molecular and cellular biology.

[9]  I. Herskowitz,et al.  Characterization of the yeast SWI1, SWI2, and SWI3 genes, which encode a global activator of transcription , 1992, Cell.

[10]  G. Felsenfeld,et al.  Chromatin as an essential part of the transcriptional mechanim , 1992, Nature.

[11]  B. Wang,et al.  The nucleosomal core histone octamer at 3.1 A resolution: a tripartite protein assembly and a left-handed superhelix. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[12]  M. Carlson,et al.  New SNF genes, GAL11 and GRR1 affect SUC2 expression in Saccharomyces cerevisiae. , 1991, Genetics.

[13]  R. Roeder,et al.  Family of proteins that interact with TFIID and regulate promoter activity , 1991, Cell.

[14]  F. Winston,et al.  Mutations in SPT16/CDC68 suppress cis- and trans-acting mutations that affect promoter function in Saccharomyces cerevisiae. , 1991, Molecular and cellular biology.

[15]  J. T. Kadonaga,et al.  Role of nucleosomal cores and histone H1 in regulation of transcription by RNA polymerase II. , 1991, Science.

[16]  R. Conaway,et al.  Initiation of eukaryotic messenger RNA synthesis. , 1991, The Journal of biological chemistry.

[17]  R. Roeder,et al.  Activation of class II gene transcription by regulatory factors is potentiated by a novel activity , 1991, Cell.

[18]  F. Winston,et al.  SPT5, an essential gene important for normal transcription in Saccharomyces cerevisiae, encodes an acidic nuclear protein with a carboxy-terminal repeat , 1991, Molecular and cellular biology.

[19]  K. Irie,et al.  SGV1 encodes a CDC28/cdc2-related kinase required for a Gα subunit-mediated adaptive response to pheromone in S. cerevisiae , 1991, Cell.

[20]  L. M. Lira,et al.  Sequence-specific antirepression of histone H1-mediated inhibition of basal RNA polymerase II transcription. , 1991, Science.

[21]  J. Workman,et al.  Activation domains of stably bound GAL4 derivatives alleviate repression of promoters by nucleosomes , 1991, Cell.

[22]  R. Young,et al.  Intragenic and extragenic suppressors of mutations in the heptapeptide repeat domain of Saccharomyces cerevisiae RNA polymerase II. , 1989, Genetics.

[23]  M. Carlson,et al.  Mutational analysis of the Saccharomyces cerevisiae SNF1 protein kinase and evidence for functional interaction with the SNF4 protein , 1989, Molecular and cellular biology.

[24]  F. Winston,et al.  SPT15, the gene encoding the yeast TATA binding factor TFIID, is required for normal transcription initiation in vivo , 1989, Cell.

[25]  R. Tjian,et al.  Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins. , 1989, Science.

[26]  J. Corden,et al.  Phosphorylation of RNA polymerase by the murine homologue of the cell-cycle control protein cdc2 , 1989, Nature.

[27]  J. M. Lee,et al.  A protein kinase that phosphorylates the C-terminal repeat domain of the largest subunit of RNA polymerase II. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[28]  M. Grunstein,et al.  Nucleosome loss activates yeast downstream promoters in vivo , 1988, Cell.

[29]  Christine Guthrie,et al.  Spliceosomal RNA U6 is remarkably conserved from yeast to mammals , 1988, Nature.

[30]  L. Guarente.  UASs and enhancers: Common mechanism of transcriptional activation in yeast and mammals , 1988, Cell.

[31]  F. Winston,et al.  Changes in histone gene dosage alter transcription in yeast. , 1988, Genes & development.

[32]  F. Winston,et al.  Isolation and analysis of a novel class of suppressor of Ty insertion mutations in Saccharomyces cerevisiae. , 1988, Genetics.

[33]  J. Broach,et al.  Autoregulation of 2μm circle gene expression provides a model for maintenance of stable plasmid copy levels , 1988, Cell.

[34]  J. Workman,et al.  Binding of transcription factor TFIID to the major late promoter during in vitro nucleosome assembly potentiates subsequent initiation by RNA polymerase II , 1987, Cell.

[35]  R. Kornberg,et al.  Nucleosomes inhibit the initiation of transcription but allow chain elongation with the displacement of histones , 1987, Cell.

[36]  F. Winston,et al.  Three genes are required for trans-activation of Ty transcription in yeast. , 1987, Genetics.

[37]  I. Herskowitz,et al.  Activation of the yeast HO gene by release from multiple negative controls , 1987, Cell.

[38]  F. Winston,et al.  The SPT6 gene is essential for growth and is required for delta-mediated transcription in Saccharomyces cerevisiae , 1987, Molecular and cellular biology.

[39]  J. Knezetic,et al.  The presence of nucleosomes on a DNA template prevents initiation by RNA polymerase II in vitro , 1986, Cell.

[40]  M. Carlson,et al.  Upstream region of the SUC2 gene confers regulated expression to a heterologous gene in Saccharomyces cerevisiae , 1985, Molecular and cellular biology.

[41]  M. Carlson,et al.  Genes affecting the regulation of SUC2 gene expression by glucose repression in Saccharomyces cerevisiae. , 1984, Genetics.

[42]  G. Fink,et al.  Mutations affecting Ty-mediated expression of the HIS4 gene of Saccharomyces cerevisiae. , 1984, Genetics.

[43]  M. Smith,et al.  Yeast H3 and H4 histone messenger RNAs are transcribed from two non-allelic gene sets. , 1983, Journal of molecular biology.

[44]  D. Botstein,et al.  The secreted form of invertase in Saccharomyces cerevisiae is synthesized from mRNA encoding a signal sequence , 1983, Molecular and cellular biology.

[45]  K. Murata,et al.  Transformation of intact yeast cells treated with alkali cations , 1983 .

[46]  D. Botstein,et al.  Two differentially regulated mRNAs with different 5′ ends encode secreted and intracellular forms of yeast invertase , 1982, Cell.

[47]  D. Botstein,et al.  Mutants of yeast defective in sucrose utilization. , 1981, Genetics.

[48]  G. Fink,et al.  Genetic events associated with an insertion mutation in yeast , 1980, Cell.

[49]  M. Grunstein.  Histone function in transcription. , 1990, Annual review of cell biology.

[50]  D. Botstein,et al.  A Saccharomyces cerevisiae genomic plasmid bank based on a centromere-containing shuttle vector. , 1987, Gene.

[51]  G. Fink,et al.  Methods in yeast genetics , 1979 .