Schizosaccharomyces pombe cells switch between two mating types, Plus (P) and Minus (M). The mating type of the cell is determined by the allele present at the mat1 locus which is transcriptionally active. mat1-P cells express the P cell-type while mat1-M cells express the M cell-type. Silent P and M genetic information is stored in a heterochromatic region linked to mat1 in respectively the mat2-P and mat3-M cassettes. Mating-type switching occurs due to replication-coupled recombination events that copy the genetic material from one of the two silent cassettes, to the transcriptionally active mat1 locus. Preferential mat1 conversion is regulated by cell type; mat2-P is used in M cells and mat3-M in P cells, a phenomenon called directionality of mating-type switching. It has been proposed by others that the directionality of mating-type switching is regulated by the cell-type specific strength of expression and binding of the Swi2 protein in the mating-type region. In the proposed model Swi2 and its associated partner Swi5 serve as a recombination promoting complex (RPC) which in P cell binds to a Swi2-dependent recombinational enhancer (SRE) adjacent to mat3-M and in M cell spreads across the heterochromatic mating-type region. This cell-type specific binding of RPC directs the recombination machinery to select mat3-M in P cell and mat2-P in M cell.
Here, I present evidence that donor choice is regulated by two portable recombination enhancers (SRE2 and SRE3) which are able to favor the choice of their adjacent silent donor cassette. These enhancers retain their function when they are moved to an ectopic location in the mat2-mat3 heterochromatic domain. Furthermore, I also show that heterochromatin plays an important role in establishing directionality by biasing competitions between the two enhancers. Together, these findings lead to a new model for the directionality of mating-type switching. In this model the competition between SRE2 and SRE3 is driven by the differential abundance of the Swi6 and Swi2 proteins in the mating-type region of P and M cells. High levels of Swi2 and Swi6 in M cell promote use of SRE2 over SRE3.
In a separate study, I found that a DNA rearrangement replacing a boundary element near mat3-M (IR-R) with a ribosomal DNA repeat (rDNA-R) also affects donor choice. mat3-M is poorly used in rDNA-R cells. Reduced use of mat3-M might result from the relocalization of the mating-type region to the nucleolus, a nuclear compartment possibly inhibitory to some forms of recombination. Alternatively, reduced use of mat3-M in rDNA-R cells, might result from transcription across SRE3. Transcription originating in rDNA-R might displace RPC from SRE3 or alter histone modifications in SRE3, reducing its ability to stimulate recombination.