Lawrence Richard J, Volpe Thomas A
Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, 303 East Chicago Avenue, Chicago, IL 60611, USA.
Proc Natl Acad Sci U S A. 2009 Jan 27;106(4):1163-8. doi: 10.1073/pnas.0811161106. Epub 2009 Jan 21.
Eukaryotic genomes can be organized into distinct domains of heterochromatin or euchromatin. In the fission yeast Schizosaccharomyces pombe, assembly of heterochromatin at the silent mating-type region is critical for cell fate determination in the form of mating-type switching. Here, we report that the ubiquitin ligase, Msc1, is a critical factor required for proper cell fate determination in S. pombe. In the absence of Msc1, the in vivo mobility of Swi6 at heterochromatic foci is compromised, and centromere heterochromatin becomes hyperenriched with the heterochromatin binding protein Swi6/HP1. However, at the mating-type locus, Swi6 recruitment is defective in the absence of Msc1. Therefore, Msc1 links maintaining dynamic heterochromatin with proper heterochromatin assembly and cell fate determination. These findings have implications for understanding mechanisms of differentiation in other organisms.
真核生物基因组可被组织成异染色质或常染色质的不同结构域。在裂殖酵母粟酒裂殖酵母中，沉默交配型区域的异染色质组装对于以交配型转换形式进行的细胞命运决定至关重要。在此，我们报道泛素连接酶Msc1是粟酒裂殖酵母中正确细胞命运决定所需的关键因子。在没有Msc1的情况下，Swi6在异染色质位点的体内移动性受损，并且着丝粒异染色质变得过度富集异染色质结合蛋白Swi6/HP1。然而，在交配型位点，在没有Msc1的情况下Swi6的募集存在缺陷。因此，Msc1将维持动态异染色质与正确的异染色质组装及细胞命运决定联系起来。这些发现对于理解其他生物体中的分化机制具有重要意义。
