Going in the Right Direction: Mating-Type Switching ofSchizosaccharomyces pombeIs Controlled by Judicious Expression of Two Differentswi2Transcripts

Abstract

Schizosaccharomyces pombe, the fission yeast, cells alternate between P-and M-mating type, controlled by the alternate alleles of the mating-type locus (mat1). The mat1 switching occurs by replacing mat1 with a copy derived from a silenced "donor locus," mat2P or mat3M. The mechanism of donor choice ensuring that switching occurs primarily and productively to the opposite type, called directionality, is largely unknown. Here we identified the mat1-Mc gene, a mammalian sex-determination gene (SRY) homolog, as the primary gene that dictates directionality in M cells. A previously unrecognized, shorter swi2 mRNA, a truncated form of the swi2, was identified, and its expression requires the mat1-Mc function. We also found that the abp1 gene (human CENPB homolog) controls directionality through swi2 regulation. In addition, we implicated a cis-acting DNA sequence in mat2 utilization. Overall, we showed that switching directionality is controlled by judicious expression of two swi2 transcripts through a cell-type-regulated dual promoter. In this respect, this regulation mechanism resembles that of the Drosophila sex-determination Slx gene.

The fission yeast CENP-B protein Abp1 prevents pervasive transcription of repetitive DNA elements

“…Originally identified as a centromere-associated protein [11–13], CENP-B is important for de novo centromere assembly in mammalian artificial chromosomes [14–18], and for heterochromatin formation and silencing in S. pombe [19]. Also in S. pombe , CENP-B contributes to silencing of Tf2 retrotransposons [20], regulates directionality of mating-type switching [21–23] and stabilizes stalled replication forks [24, 25]. Our results show that loss of abp1 results in the accumulation of CUTs.…”

A Unique DNA Recombination Mechanism of the Mating/Cell-type Switching of Fission Yeasts: a Review

“…The Mc protein, a transcription factor encoded within the M cassette, provides proper distribution of the RPC by positively regulating the expression of swi2 and swi5 genes in M cells (57). In addition, Mc stimulates expression of a shorter transcript (swi2S) of the swi2 gene that facilitates mat2 utilization in M cells (58). However, in conflict with the spreading hypothesis, another study suggests that Swi2 binds directly to the mat2 cis-acting element in M cells (53).…”

“…Swi2 binding to the mat region requires the SRE3, and it was proposed that in M cells Swi2 would reach to the mat2 region by spreading from the SRE3 through a heterochromatin region between mat2 and mat3 via physical interaction with Swi6 (54). Two more proteins, Abp1 and Mc, are required for Swi2 binding to the mat2 region, perhaps by promoting Swi2 spreading (56,57,58). The Mc protein, a transcription factor encoded within the M cassette, provides proper distribution of the RPC by positively regulating the expression of swi2 and swi5 genes in M cells (57).…”

Two Portable Recombination Enhancers Direct Donor Choice in Fission Yeast Heterochromatin

“…Both elements are A-T rich (75% for SRE2 and 72% for SRE3 over 492 bp). The authors of a recent study [51] noticed like us that a deletion adjacent to mat2-P prevented efficient use of mat2-P however the study did not characterize the element further. Several observations reported below argue against deletion of SRE2 simply preventing use of mat2 as a donor.…”

“…A recent addition to the model proposes that the spreading is driven by a greater abundance of the Swi2 and Swi5 proteins in M cells resulting from the positive regulation of the swi2 and swi5 genes by the M-specific transcription factor Mc [50]. Alternatively, Mc might stimulate the production of a shorter form of Swi2 expressed in P cells through alternative promoter usage [51].…”