Olsson T G, Ekwall K, Allshire R C, Sunnerhagen P, Partridge J F, Richardson W A
Department of Molecular Biology, Lundberg Laboratory, Göteborg University, PO Box 462, S-405 30 Göteborg, Sweden.
Nucleic Acids Res. 1998 Jul 1;26(13):3247-54. doi: 10.1093/nar/26.13.3247.
hda1+ (histone deacetylase 1) is a fission yeast gene which is highly similar in sequence to known histone deacetylase genes in humans and budding yeast. We have investigated if this putative histone deacetylase contributes to transcriptional silencing in the fission yeast Schizosaccharomyces pombe. A precise deletion allele of the hda1+ open reading frame was created. Cells lacking the hda1+ gene are viable. However, genetic analysis reveals that cells without hda1 + display enhanced gene repression/silencing of marker genes, residing adjacent to telomeres, close to the silent mating-type loci and within centromere I. This phenotype is very similar to that recently reported for rpd3 mutants both in Drosophila and budding yeast. No defects in chromosome segregation or changes in telomere length were detected. Cells lacking the hda1+ gene display reduced sporulation. Growth of hda1 cells is partially inhibited by low concentrations of Trichostatin A (TSA), a known inhibitor of histone deacetylase enzymes. TSA treatment is also able to overcome the enhanced silencing found in heterochromatic regions of hda1 cells. These results indicate a genetic redundancy with respect to deacetylase genes and partially overlapping functions of these in fission yeast. The significance of these results is discussed in the light of recent discoveries from other eukaryotes.
hda1+（组蛋白去乙酰化酶1）是一种裂殖酵母基因，其序列与人类和芽殖酵母中已知的组蛋白去乙酰化酶基因高度相似。我们研究了这种假定的组蛋白去乙酰化酶是否有助于裂殖酵母粟酒裂殖酵母中的转录沉默。创建了hda1+开放阅读框的精确缺失等位基因。缺乏hda1+基因的细胞是可行的。然而，遗传分析表明，没有hda1+的细胞对位于端粒附近、靠近沉默交配型位点和着丝粒I内的标记基因表现出增强的基因抑制/沉默。这种表型与最近在果蝇和芽殖酵母中报道的rpd3突变体的表型非常相似。未检测到染色体分离缺陷或端粒长度变化。缺乏hda1+基因的细胞显示出孢子形成减少。低浓度的曲古抑菌素A（TSA）（一种已知的组蛋白去乙酰化酶抑制剂）部分抑制了hda1细胞的生长。TSA处理也能够克服在hda1细胞异染色质区域发现的增强的沉默。这些结果表明在裂殖酵母中去乙酰化酶基因存在遗传冗余，并且它们的功能部分重叠。根据其他真核生物的最新发现讨论了这些结果的意义。
