Epigenetic inheritance of transcriptional states in S. cerevisiae

SIR1, one of several genes required for repression of yeast silent mating type loci, has a unique role in repression of the HML alpha locus. Single-cell assays revealed that cells with mutant alleles of SIR1, including presumptive null alleles, existed as populations of genetically identical cells whose members were in one of two different regulatory states. A minority of cells had a repressed HML alpha locus whereas the majority had a derepressed HML alpha locus. The two states were mitotically stable, although rare changes in state were observed during mitotic growth, possibly reflecting heritable changes to the HML alpha locus at or before replication. Analysis of changes in state suggests that SIR1 protein has a role in the establishment but not the maintenance of repression of silent mating type genes, whereas SIR2, SIR3, and SIR4 are required for maintenance.

[1]  R Holliday,et al.  The inheritance of epigenetic defects. , 1987, Science.

[2]  M. Ptashne A Genetic Switch , 1986 .

[3]  R. Umek,et al.  New beginnings in studies of eukaryotic DNA replication origins. , 1989, Biochimica et biophysica acta.

[4]  I. Herskowitz,et al.  Life cycle of the budding yeast Saccharomyces cerevisiae. , 1988, Microbiological reviews.

[5]  K. Arai,et al.  Nucleotide sequences of STE2 and STE3, cell type‐specific sterile genes from Saccharomyces cerevisiae , 1985, The EMBO journal.

[6]  H. Weintraub Assembly and propagation of repressed and derepressed chromosomal states , 1985, Cell.

[7]  I. Herskowitz,et al.  Asymmetry and directionality in production of new cell types during clonal growth: the switching pattern of homothallic yeast , 1979, Cell.

[8]  G. Saari,et al.  Multiple regulation of STE2, a mating-type-specific gene of Saccharomyces cerevisiae , 1986, Molecular and cellular biology.

[9]  François Jacob,et al.  Regulation of Repressor Expression in λ , 1970 .

[10]  A. D. Kaiser Mutations in a temperate bacteriophage affecting its ability to lysogenize Escherichia coli. , 1957, Virology.

[11]  K. Nasmyth The regulation of yeast mating-type chromatin structure by SIR: An action at a distance affecting both transcription and transposition , 1982, Cell.

[12]  W. L. Fangman,et al.  The localization of replication origins on ARS plasmids in S. cerevisiae , 1987, Cell.

[13]  Donald D. Brown The role of stable complexes that repress and activate eucaryotic genes , 1984, Cell.

[14]  H. Cedar DNA methylation and gene activity , 1988, Cell.

[15]  I. Herskowitz,et al.  Interconversion of Yeast Mating Types III. Action of the Homothallism (HO) Gene in Cells Homozygous for the Mating Type Locus. , 1977, Genetics.

[16]  J. Rine,et al.  Roles of two DNA‐binding factors in replication, segregation and transcriptional repression mediated by a yeast silencer. , 1988, The EMBO journal.

[17]  L. Breeden,et al.  Characterization of a “silencer” in yeast: A DNA sequence with properties opposite to those of a transcriptional enhancer , 1985, Cell.

[18]  R. Rothstein One-step gene disruption in yeast. , 1983, Methods in enzymology.

[19]  R Holliday,et al.  DNA modification mechanisms and gene activity during development , 1975, Science.

[20]  V. Mackay,et al.  Saccharomyces cerevisiae: A Diffusible Sex Factor , 1970, Science.

[21]  M. Delbrück,et al.  Mutations of Bacteria from Virus Sensitivity to Virus Resistance. , 1943, Genetics.

[22]  A. Wolffe,et al.  Developmental regulation of two 5S ribosomal RNA genes. , 1988, Science.

[23]  K. Nasmyth,et al.  The role of DNA replication in the repression of the yeast mating-type silent loci. , 1984, Cold Spring Harbor symposia on quantitative biology.

[24]  C. Laird Proposed mechanism of inheritance and expression of the human fragile-X syndrome of mental retardation. , 1987, Genetics.

[25]  J. Hicks,et al.  Cloning and characterization of four SIR genes of Saccharomyces cerevisiae , 1986, Molecular and cellular biology.

[26]  L. Hartwell,et al.  The C-terminus of the S. cerevisiae α-pheromone receptor mediates an adaptive response to pheromone , 1988, Cell.

[27]  A. Novick,et al.  ENZYME INDUCTION AS AN ALL-OR-NONE PHENOMENON. , 1957, Proceedings of the National Academy of Sciences of the United States of America.

[28]  V. Mackay,et al.  Physiology of mating in three yeasts. , 1977, Advances in microbial physiology.

[29]  M. Grunstein,et al.  Extremely conserved histone H4 N terminus is dispensable for growth but essential for repressing the silent mating loci in yeast , 1988, Cell.

[30]  C. A. Bilinski,et al.  Induction of Normal Ascosporogenesis in Two-Spored Saccharomyces cerevisiae by Glucose, Acetate, and Zinc , 1980, Journal of bacteriology.

[31]  I. Herskowitz,et al.  Four genes responsible for a position effect on expression from HML and HMR in Saccharomyces cerevisiae. , 1987, Genetics.

[32]  G. Sprague,,et al.  Induction of the yeast α-specific STE3 gene by the peptide pheromone a-factor , 1984 .

[33]  J. Strathern,et al.  Regulation of mating-type information in yeast. Negative control requiring sequences both 5' and 3' to the regulated region. , 1984, Journal of molecular biology.

[34]  I. Herskowitz,et al.  A suppressor of mating-type locus mutations in Saccharomyces cerevisiae: evidence for and identification of cryptic mating-type loci. , 1979, Genetics.

[35]  R. McCarroll,et al.  Time of replication of yeast centromeres and telomeres , 1988, Cell.

[36]  J. Rine,et al.  A position effect on the expression of a tRNA gene mediated by the SIR genes in Saccharomyces cerevisiae , 1986, Molecular and cellular biology.

[37]  J. Thorner,et al.  The STE2 gene product is the ligand-binding component of the alpha-factor receptor of Saccharomyces cerevisiae. , 1988, The Journal of biological chemistry.

[38]  V. Mackay,et al.  Mutations affecting sexual conjugation and related processes in Saccharomyces cerevisiae. I. Isolation and phenotypic characterization of nonmating mutants. , 1974, Genetics.

[39]  I. Herskowitz,et al.  Control of Cell Type in Saccharomyces cerevisiae: Mating Type and Mating-type Interconversion , 1981 .

[40]  I. Herskowitz,et al.  Interconversion of Yeast Mating Types II. Restoration of Mating Ability to Sterile Mutants in Homothallic and Heterothallic Strains. , 1977, Genetics.

[41]  I. Herskowitz,et al.  The lysis-lysogeny decision of phage lambda: explicit programming and responsiveness. , 1980, Annual review of genetics.

[42]  J. Broach,et al.  Identification of sites required for repression of a silent mating type locus in yeast. , 1984, Journal of molecular biology.

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

[44]  R. Doolittle,et al.  Phase variation: evolution of a controlling element. , 1980, Science.

[45]  Susumu,et al.  Identification and characterization of genes and mutants for an N‐terminal acetyltransferase from yeast. , 1989, The EMBO journal.

[46]  M. Johnston,et al.  Mutational analysis of the GAL4-encoded transcriptional activator protein of Saccharomyces cerevisiae. , 1988, Genetics.

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

[48]  J. Thorner,et al.  The yeast ARD1 gene product is required for repression of cryptic mating-type information at the HML locus , 1987, Molecular and cellular biology.

[49]  K. Nasmyth,et al.  Role of DNA replication in the repression of silent mating type loci in yeast , 1984, Nature.

[50]  C. Newlon,et al.  Time of replication of ARS elements along yeast chromosome III , 1989, Molecular and cellular biology.