Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Proc Natl Acad Sci U S A. 2011 Nov 15;108(46):18754-9. doi: 10.1073/pnas.1109988108. Epub 2011 Oct 31.
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, cell-type-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.
裂殖酵母细胞通过用来自 mat2-P 或 mat3-M 沉默供体基因座的序列替换表达的 mat1 基因座的遗传信息来转换交配型。供体基因座的选择由细胞类型决定,使得 mat2 是 M 细胞的首选供体,而 mat3 是 P 细胞的首选供体。供体选择涉及包含 Swi2 和 Swi5 的重组促进复合物 (RPC)。在 P 细胞中,RPC 定位于位于 mat3 附近的特定 DNA 元件,但在 M 细胞中,它扩展到沉默的交配型区域,包括 mat2-P。RPC 的这种差异分布调节了供体的非随机选择。然而,RPC 定位的细胞类型特异性差异尚不清楚。在这里,我们表明 mat1-M 编码的因子 Mc 与雄性性别决定因子 SRY 具有结构和功能上的相似性,它在 swi2 和 swi5 基因座高度富集,并促进 RPC 成分的高水平表达。Mc 的缺失将 Swi2 和 Swi5 降低到与 P 细胞相当的水平,并破坏了 RPC 在 mat2/3 区域的扩展。Mc 还定位于在 M 细胞中优先表达的基因座和逆转录转座子 LTRs。我们证明了 Mc 在 LTRs 和 swi2 上的定位需要 Abp1,这是转座子衍生的 CENP-B 蛋白的同源物,并且 Abp1 的缺失会损害 Swi2 蛋白表达和供体选择机制。这些结果表明 Mc 调节重组因子的水平,这对于交配型供体选择以及减数分裂中观察到的偏基因转换很重要,其中 M 细胞作为遗传信息的优先供体。