Aguilar-Arnal Lorena, Marsellach Francesc-Xavier, Azorín Fernando
Institute of Molecular Biology of Barcelona, CSIC, Parc Científic de Barcelona, Barcelona, Spain.
EMBO J. 2008 Apr 9;27(7):1029-38. doi: 10.1038/emboj.2008.53. Epub 2008 Mar 20.
In fission yeast, mating-type switching involves replacing genetic information contained at the expressed mat1 locus by that of either the mat2P or mat3M donor loci. Donor selection is nonrandom, as mat1P cells preferentially use mat3M for switching, whereas mat1M cells use mat2P. Switching directionality is determined by the cell-type-specific distribution of the Swi2-Swi5 complex that, in mat1P cells, localises to mat3M and, only in mat1M cells, spreads to mat2P in a heterochromatin-dependent manner. Mechanisms regulating spreading of Swi2-Swi5 across heterochromatin are not fully understood. Here, we show that the fission yeast homologue of CENP-B, Abp1, binds to the silent domain of the mating-type locus and regulates directionality of switching. Deletion of abp1 prevents utilisation of mat2P, as when heterochromatin is disrupted and spreading of Swi2-Swi5 is impaired. Our results show that, indeed, deletion of abp1 abolishes spreading of Swi2-Swi5 to mat2P. However, in abp1Delta cells, heterochromatin organisation at the mating-type locus is preserved, indicating that Abp1 is actually required for efficient spreading of Swi2-Swi5 through heterochromatin. Cbh1 and Cbh2, which are also homologous to CENP-B, have only a minor contribution to the regulation of directionality of switching, which is in contrast with the strong effects observed for Abp1.
在裂殖酵母中,交配型转换涉及用mat2P或mat3M供体位点的遗传信息替换位于表达的mat1位点的遗传信息。供体选择是非随机的,因为mat1P细胞优先使用mat3M进行转换,而mat1M细胞使用mat2P。转换方向性由Swi2-Swi5复合物的细胞类型特异性分布决定,在mat1P细胞中,该复合物定位于mat3M,并且仅在mat1M细胞中,以异染色质依赖性方式扩散到mat2P。调节Swi2-Swi5在异染色质上扩散的机制尚未完全了解。在这里,我们表明CENP-B的裂殖酵母同源物Abp1与交配型位点的沉默结构域结合并调节转换的方向性。缺失abp1会阻止mat2P的利用,就像异染色质被破坏且Swi2-Swi5的扩散受损时一样。我们的结果表明,确实,缺失abp1会消除Swi2-Swi5向mat2P的扩散。然而,在abp1Δ细胞中,交配型位点的异染色质组织得以保留,这表明Abp1实际上是Swi2-Swi5通过异染色质有效扩散所必需的。与Cbh1和Cbh2也与CENP-B同源,它们对转换方向性的调节作用较小,这与观察到的Abp1的强烈作用形成对比。