α2p controls donor preference during mating type interconversion in yeast by inactivating a recombinational enhancer of chromosome III

Szeto, Lisa; Fafalios, Maria K.; Zhong, Hualin; Vershon, Andrew K.; Broach, James R.

doi:10.1101/gad.11.15.1899

Cited by 51 publications

(66 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The seventh position occupied by ␣2 in the ␣ strain corresponds to a reporter gene, containing ␣2-Mcm1-binding sites, that was integrated at the URA3 locus as a positive control. The eighth position corresponds to two adjacent ␣2-Mcm1-binding sites (termed DPS1͞DPS2) that regulate a recombinational enhancer involved in the gene-conversion events that underlie mating-type interconversion (17,18).…”

Section: Results A-specific Genes (Genes Repressed By ␣2-mcm1)mentioning

confidence: 99%

Genomic dissection of the cell-type-specification circuit in Saccharomyces cerevisiae

Galgoczy

Cassidy-Stone

Llinás

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

100

102

View full text Add to dashboard Cite

The budding yeast Saccharomyces cerevisiae has three cell types (a cells, ␣ cells, and a͞␣ cells), each of which is specified by a unique combination of transcriptional regulators. This transcriptional circuit has served as an important model for understanding basic features of the combinatorial control of transcription and the specification of cell type. Here, using genome-wide chromatin immunoprecipitation, transcriptional profiling, and phylogenetic comparisons, we describe the complete cell-type-specification circuit for S. cerevisiae. We believe this work represents a complete description of cell-type specification in a eukaryote.chromatin immunoprecipitation ͉ mating ͉ transcriptional circuit A problem of central importance in understanding multicellular organisms is how different cell types are stably maintained. Typically, cell-type specification is based on a transcriptional circuit in which combinations of regulatory proteins determine the final pattern of gene expression that is appropriate to a given cell type. Although unicellular, the yeast Saccharomyces cerevisiae has three distinct types of cells, and the cell-specification circuit is combinatorial (refs. 1-3 and Fig. 1). The a and ␣ cell types are typically haploid in DNA content and mate with each other in an elaborate ritual that culminates in cellular and nuclear fusion. These events produce the third type of cell, the a͞␣ cell type, which is typically diploid. This cell type cannot mate but, when environmental conditions are appropriate, can undergo meiosis and sporulation, producing two a and two ␣ cell types. The patterns of cell-type-specific gene expression are set up by a few sequence-specific DNA-binding proteins acting in various combinations. Three critical proteins (␣1, ␣2, and a1) are encoded by the mating-type (MAT) locus. A fourth key sequence-specific DNA-binding protein (Mcm1) is encoded elsewhere in the genome. In this article we use the term ''cell-type-specification circuit'' to refer to the regulatory scheme diagrammed in Fig. 1, because each component and branch of this scheme is necessary and sufficient to establish and maintain three cell types.In this article we apply three methods [genome-wide chromatin immunoprecipitation (ChIP), genome-wide transcriptional profiling, and phylogenetic comparisons] in an attempt to completely determine the cell-type-specification circuit in S. cerevisiae (4-8). The use of three different techniques generated considerably more data than are needed to reconstruct the circuit, and because it is overdetermined, we believe our circuit description to be very accurate, containing at most only a few false negatives or positives. Figs. 3, 5 A and B, and 6. EG123, yDG208, and yDG240 are all derivatives of S288C. For the salt-sensitivity experiment, the a1-␣2 site in the endogenous HOG1 gene promoter was replaced by integration of Kluyveromyces lactis URA3, which was subsequently replaced by the integration of an oligonucleotidegenerated construct to restore the HOG1 promoter with a modified a1-...

show abstract

Section: Results A-specific Genes (Genes Repressed By ␣2-mcm1)mentioning

confidence: 99%

Genomic dissection of the cell-type-specification circuit in Saccharomyces cerevisiae

Galgoczy

Cassidy-Stone

Llinás

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

100

102

View full text Add to dashboard Cite

show abstract

“…Examples of such recombination events include the lineage and developmental stage-specific V(D)J recombination in the immune system of mammals (1) and mating-type switching in the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe (2)(3)(4)(5). In these distantly related yeast species, cells alternate between two distinct mating-type alleles by copying genetic information from one of the two silent donor loci to the active mating-type locus via highly orchestrated recombination processes (6)(7)(8).…”

mentioning

confidence: 99%

A homolog of male sex-determining factor SRY cooperates with a transposon-derived CENP-B protein to control sex-specific directed recombination

Matsuda

Sugioka-Sugiyama

Mizuguchi

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Schizosaccharomyces pombe cells switch mating type by replacing genetic information at the expressed mat1 locus with sequences copied from mat2-P or mat3-M silent donor loci. The choice of donor locus is dictated by cell type, such that mat2 is the preferred donor in M cells and mat3 is the preferred donor in P cells. Donor choice involves a recombination-promoting complex (RPC) containing Swi2 and Swi5. In P cells, the RPC localizes to a specific DNA element located adjacent to mat3, but in M cells it spreads across the silent mating-type region, including mat2-P. This differential distribution of the RPC regulates nonrandom choice of donors. However, celltype-specific differences in RPC localization are not understood. Here we show that the mat1-M-encoded factor Mc, which shares structural and functional similarities with the male sex-determining factor SRY, is highly enriched at the swi2 and swi5 loci and promotes elevated levels of RPC components. Loss of Mc reduces Swi2 and Swi5 to levels comparable to those in P cells and disrupts RPC spreading across the mat2/3 region. Mc also localizes to loci expressed preferentially in M cells and to retrotransposon LTRs. We demonstrate that Mc localization at LTRs and at swi2 requires Abp1, a homolog of transposon-derived CENP-B protein and that loss of Abp1 impairs Swi2 protein expression and the donor choice mechanism. These results suggest that Mc modulates levels of recombination factors, which is important for mating-type donor selection and for the biased gene conversion observed during meiosis, where M cells serve as preferential donors of genetic information. (1) and mating-type switching in the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe (2-5). In these distantly related yeast species, cells alternate between two distinct mating-type alleles by copying genetic information from one of the two silent donor loci to the active mating-type locus via highly orchestrated recombination processes (6-8).The mating-type region of S. pombe contains three linked locimat1, mat2, and mat3-located on chromosome 2. In wild-type homothallic strains, designated h 90 , mat2 is located ∼17 kb centromere-distal to mat1, whereas mat3 is separated from mat2 by an 11-kb interval ( Fig. 1) (8, 9). The mating type of a haploid cell is determined by the presence of P or M information at mat1 (8). Each allele consists of two divergently transcribed genes (10). mat1-P contains the Pc and Pi genes, and mat1-M contains the Mc and Mi genes. mat2 and mat3 contain the same genetic information as mat1-P and mat1-M, respectively, but are maintained in a silent state. These silent mating-type cassettes are embedded in a 20-kb heterochromatin domain surrounded by inverted repeat (IR-R and IR-

show abstract

“…A clear example of DNase I sensitivity that correlates with active regions of chromatin and contrasts with chromatin that is silenced is found in the RE, where the two Mat␣2p/Mcm1p binding sites are DNase I sensitive in a cells but less sensitive or not sensitive, for ␣2#1 or ␣2#2, respectively, as part of an organized chromatin domain in ␣ cells. The correlation of chromatin structure with transcription of the silent RNAs from the RE is clear, where in a cells the silent RNAs are transcribed downstream of the both operators but not in ␣ cells (23).…”

Section: Discussionmentioning

confidence: 94%

“…In contrast to these similarities, a new DNase I-sensitive site (highlighted with a dot on the right side of the mapping picture) appeared early in the switching process, increased in susceptibility, and then faded away as the switching process was completed. The site was located just to the right of the ␣2#2 operator, downstream from the transcription start sites for one of the three noncoding RNAs transcribed from the recombination enhancer, identified by Szeto et al (23). At the end of switching, the RE chromatin must be remodeled from the a-cell structure, characterized by hypersensitive sites, to the ␣-cell array of positioned nucleosomes.…”

Section: Resultsmentioning

confidence: 99%

“…Repair of this break in an ␣ cell preferentially uses silent matingtype information encoded at HMRa, while in an a cell, recombination usually takes place with sequences located at HML␣ (4). The recombination enhancer (RE), located ϳ30,000 bp from the left end of chromosome III and highly conserved between yeast species, controls this directionality (23,33,34,36). In a cells, the RE has nuclease-hypersensitive sites indicating unusual DNA geometry and footprints suggesting protein binding sites.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Global Chromatin Structure of 45,000 Base Pairs of Chromosome III in a- and α-Cell Yeast and during Mating-Type Switching

Ercan

Simpson

2004

Molecular and Cellular Biology

View full text Add to dashboard Cite

Directionality of yeast mating-type switching has been attributed to differences in chromatin structure for the left arm of chromosome III. We have mapped the structure of ϳ45 kbp of the left arm of chromosome III in a and ␣ cells in logarithmically growing cultures and in a cells during switching. Distinctive features of chromatin structure were the occurrence of DNase I-hypersensitive sites in the promoter region of nearly every gene and some replication origins and the presence of extended regions of positioned nucleosomes in ϳ25% of the open reading frames. Other than the recombination enhancer, chromatin structures were identical in the two cell types. Changes in chromatin structure during switching were confined to the recombination enhancer. This unbiased analysis of an extended region of chromatin reveals that significant features of organized chromatin exist for the entire region, and these features are largely static with respect to mating type and mating-type switching. Our analysis also shows that primary chromatin structure does not cause the documented differences in recombinational frequency of the left arm of chromosome III in yeast a and ␣ cells.Mating-type interconversion in Saccharomyces cerevisiae is directional. HO endonuclease initiates switching by making a double-strand cut at the MAT locus on chromosome III. Repair of this break in an ␣ cell preferentially uses silent matingtype information encoded at HMRa, while in an a cell, recombination usually takes place with sequences located at HML␣ (4). The recombination enhancer (RE), located ϳ30,000 bp from the left end of chromosome III and highly conserved between yeast species, controls this directionality (23,33,34,36). In a cells, the RE has nuclease-hypersensitive sites indicating unusual DNA geometry and footprints suggesting protein binding sites. Some of the protein candidates which may create these footprints are the two transcription activators, Fkh1p and Fkh2p, and their associated protein, Ndd1p, which were shown to bind to the RE directly only in a cells (22). In ␣ cells, organized chromatin abutting the binding site for Mcm1p and Mat␣2p replaces the active a-cell configuration (28). How these structural differences at the RE facilitate interactions between MAT and HML␣ in a cells is not known. It is known, however, that extensive segments of the left arm of chromosome III are altered in their recombination properties in the two cell types. In a cells, at least 40 kbp at the left end of this chromosome is in a hyperactive state for recombination, while over 100 kbp in this region is recombinationally "cold" in ␣ cells (35).Alterations in chromatin structure have been invoked as a possible explanation of these differences in recombination potential (35). Chromatin structure of only two regions of chromosome III has been reported. RE structures are strikingly different in ␣ and a cells. HML has a distinctive chromatin structure, but it is identical in the two cell types (29). Differences in the chromatin structures of the left arm ...

show abstract

α2p controls donor preference during mating type interconversion in yeast by inactivating a recombinational enhancer of chromosome III

Cited by 51 publications

References 42 publications

Genomic dissection of the cell-type-specification circuit in Saccharomyces cerevisiae

Genomic dissection of the cell-type-specification circuit in Saccharomyces cerevisiae

A homolog of male sex-determining factor SRY cooperates with a transposon-derived CENP-B protein to control sex-specific directed recombination

Global Chromatin Structure of 45,000 Base Pairs of Chromosome III in a- and α-Cell Yeast and during Mating-Type Switching

Contact Info

Product

Resources

About