Yeast Mating-type Genes Research Articles

The positioning of yeast telomeres depends on SIR3, SIR4, and the integrity of the nuclear membrane.

In the yeast Saccharomyces cerevisiae, transcriptional repression at the silent mating-type loci HML and HMR and at telomeres has many of the hallmarks of position-effect variegation in Drosophila, where the condensed higher-order structure of heterochromatin “spreads” into adjacent chromatin, inactivating nearby genes (for review, see Sandell and Zakian 1992). The yeast mating-type genes have provided a genetically tractable system to identify trans-acting factors and cis-acting sequences required for this repression mechanism (for review, see Laurenson and Rine 1992). In particular, deletion studies have identified a cis-acting silencer with a minimal size of 134 bp, which is required for the repression of transcription of the mating-type genes at HMR (Brand et al. 1987). Similar elements have been mapped at HML (Mahoney and Broach 1989). Like enhancers, these silencers function in either orientation and at variable distances from the targeted promoter. A number of trans-acting factors are implicated in the mechanism of...

Theoretical mechanisms for synthesis of carcinogen-induced embryonic proteins: XXVI evolutionary significance of carcinogen-induced embryonic gene activity

Besides the major theme of this series of writings—that chemically derepressed embryonic genes are fundamental to the mechanisms of carcinogenesis, there appear to be other significant aspects to this process. Yeast cells have the ability to differentially respond to carcinogens and non-carcinogens by the activation of embryonic type genes that are also found in mammals. This strange relationship is interpreted here as being due to certain phylogetically conserved genes from yeasts existing also in mammals that are used in both organisms for the same process. For example, a protooncogene found in yeast cells or embryonic cells serves for rapid mitosis. Also yeast mating type genes have high homologies to homeotic domains and therefore may be prototype genes of homeotic genes, which are embryonic type genes in animals.

Striking Similarities between the Regulatory Mechanisms Governing Yeast Mating-Type Genes and Mammalian Major Histocompatibility Complex Genes

Expression of a mammalian major histocompatibility complex (MHC) class I gene is in part regulated by a silencer DNA sequence element which binds a complex of silencer factors. This negative regulatory system is shown to be strikingly similar to the yeast alpha 2 mating-type repression system. A moderate DNA sequence homology exists between the MHC class I silencer DNA element and the yeast alpha 2 operator. Mammalian silencer factors specifically bind to the yeast alpha 2 operator DNA and also specifically interact with a yeast alpha 2-binding protein. Furthermore, the alpha 2 operator functions as a silencer element in mammalian cells when placed upstream of a MHC class I promoter.

Striking similarities between the regulatory mechanisms governing yeast mating-type genes and mammalian major histocompatibility complex genes.

Expression of a mammalian major histocompatibility complex (MHC) class I gene is in part regulated by a silencer DNA sequence element which binds a complex of silencer factors. This negative regulatory system is shown to be strikingly similar to the yeast alpha 2 mating-type repression system. A moderate DNA sequence homology exists between the MHC class I silencer DNA element and the yeast alpha 2 operator. Mammalian silencer factors specifically bind to the yeast alpha 2 operator DNA and also specifically interact with a yeast alpha 2-binding protein. Furthermore, the alpha 2 operator functions as a silencer element in mammalian cells when placed upstream of a MHC class I promoter.

Striking similarities between the regulatory mechanisms governing yeast mating-type genes and mammalian major histocompatibility complex genes J.D. Weissman and D.S. Singer Mol. Cell. Biol. 11, 4228–4234

Striking similarities between the regulatory mechanisms governing yeast mating-type genes and mammalian major histocompatibility complex genes J.D. Weissman and D.S. Singer Mol. Cell. Biol. 11, 4228–4234

Characterization of two genes required for the position-effect control of yeast mating-type genes.

The mating type of haploid yeast (a or alpha) is determined by information present at the MAT locus. Identical copies of a and alpha information are present at distal loci (HMR and HML), but transcription of these copies is repressed by the action, in trans, of four unlinked genes called SIR (silent information regulator). Repression by SIR also requires, in cis, DNA sequences called E which are found to the left of HML and HMR (but not MAT) and are greater than 1 kb from the mating-type gene promoters. SIR control can act on other promoters when they are brought near the E sequence, and thus the SIR gene products act in some general manner to repress transcription. We have determined the DNA sequence of two fragments which complement mutations in the SIR2 and SIR3 genes and show that these contain the structural genes by mapping the cloned sequences onto the yeast chromosome. The SIR2 and SIR3 coding sequences were identified by constructing gene disruptions and using these mutations to replace the normal chromosomal copies. Such null mutants of both SIR2 and SIR3 are defective in the position-effect control of the silent loci but have no other detectable phenotype. We have mapped the 5' and 3' ends of the SIR2 and SIR3 mRNAs and show that their level is unaffected by mutations in any of the four known SIR complementation groups.

Transposition of a tandem duplication of yeast mating-type genes

The switching of mating-type genes in both homothallic and heterothallic strains of the yeast Saccharomyces cerevisiae involves a site-specific transposition event1–3. A sequence at the mating-type locus (MAT) is replaced by a copy of a or α information from the unexpressed, loci, HML or HMR. Although MATa and MATα contain unique sequences of ∼700 base pairs (bp), they are flanked by sequences that are also found at HML and HMR4,5 (Fig. 1a). Recent results6–8 have suggested that the switching of MAT alleles involves an intrachromosomal mitotic gene conversion event, in which a donor sequence at HML or HMR pairs with the homologous sequences at the MAT locus. On this view the switching of mating-type information must be able to accommodate the region of non-homology in a heteroduplex structure. (Analogous gene conversions of non-homologous regions have been well documented during meiosis at MAT and for deletions in other yeast genes9,10.) One prediction of a gene conversion mechanism is that it should be possible to transpose a tandem duplication of mating-type genes from HMR to MAT. In such a switch, pairing would occur between MAT and homologous sequences flanking the two copies of the tandem duplication at HMR. Our results reported here demonstrate that a tandem duplication created at HMR by recombinant DNA techniques can be transposed to MAT without the loss of these sequences at the donor locus.

A position-effect control for gene transposition: State of expression of yeast mating-type genes affects their ability to switch

Mating-type switches of the yeast Saccharomyces cerevisiae occur by unidirectional transposition of copies of unexpressed mating-type genetic information, residing at HML and HMR loci, into the expressed MAT locus. The HML and HMR loci remain unchanged. In contrast, in appropriate strains where the silent loci are also allowed to express, for example in mar mutants, efficient switches of HML and HMR are shown to occur at rates equivalent to those observed for MAT. Thus the position-effect control on the direction of transposition is affected by the state of expression of the locus under study; the expressed loci switch regardless of their location.

Homothallic conversions of yeast mating-type genes occur by intrachromosomal recombination

The switching of yeast mating-type alleles involves a transposition of a copy of a sequence from HML or HMR to replace the sequences at MAT. Using diploid strains of yeast we have discovered that about 1% of the homothalic conversions of MAT alleles are accompanied by large intrachromosomal rearrangements. These rearrangements are highly specific fusions of part of MAT either with HMR (to produce a large recessive lethal deletion) or with HML (to produce a deficiency ring chromosome). We conclude that the mechanism of MAT conversions involves a highly specific pairing between the homologous sequences at MAT and the donor genes HML or HMR followed by a specialized gene conversion event, in which the original allele is replaced by a sequence copied from HMR or HML. At about a 1% frequency conversion of the MAT locus is accompanied by a reciprocal recombination event that results in an intrachromosomal deletion. This same preferential pairing is reflected in a high frequency (>10 −3) of site-specific mitotic recombination between MAT alleles on different chromosomes. A gene conversion model also allows us to explain the “illegal” transpositions of MAT alleles to HMR or HML that occur when normal excision of MAT is prevented.