Hansen Klavs R, Ibarra Pablo Tejero, Thon Geneviève
Department of Genetics, Institute of Molecular Biology and Physiology, University of Copenhagen, Denmark.
Nucleic Acids Res. 2006 Jan 10;34(1):78-88. doi: 10.1093/nar/gkj415. Print 2006.
In Schizosaccharomyces pombe the RNAi machinery and proteins mediating heterochromatin formation regulate the transcription of non-coding centromeric repeats. These repeats share a high sequence similarity with telomere-linked helicase (tlh) genes, implying an ancestral relationship between the two types of elements and suggesting that transcription of the tlh genes might be regulated by the same factors as centromeric repeats. Indeed, we found that mutants lacking the histone methyltransferase Clr4, the Pcu4 cullin, Clr7 or Clr8, accumulate high levels of tlh forward and reverse transcripts. Mutations and conditions perturbing histone acetylation had similar effects further demonstrating that the tlh genes are normally repressed by heterochromatin. In contrast, mutations in the RNAi factors Dcr1, Ago1 or Rdp1 led only to a modest derepression of the tlh genes indicating an alternate pathway recruits heterochromatin components to telomeres. The telomere-binding protein Taz1 might be part of such a redundant pathway, tlh transcripts being present at low levels in Deltataz1 mutants and at higher levels in Deltataz1 Deltadcr1 double mutants. Surprisingly, the chromodomain protein Chp1, a component of the Ago1-containing RITS complex, contributes more to tlh repression than Ago1, indicating the repressive effects of Chp1 are partially independent of RITS. The tlh genes are found in the subtelomeric regions of several other fungi raising the intriguing possibility of conserved regulation and function.
在粟酒裂殖酵母中，RNA干扰机制和介导异染色质形成的蛋白质调节非编码着丝粒重复序列的转录。这些重复序列与端粒连接解旋酶（tlh）基因具有高度的序列相似性，这意味着这两种元件之间存在祖先关系，并表明tlh基因的转录可能受与着丝粒重复序列相同的因素调控。事实上，我们发现缺乏组蛋白甲基转移酶Clr4、Pcu4泛素连接酶、Clr7或Clr8的突变体积累了高水平的tlh正向和反向转录本。干扰组蛋白乙酰化的突变和条件也有类似的效果，进一步证明tlh基因通常受异染色质抑制。相比之下，RNA干扰因子Dcr1、Ago1或Rdp1的突变仅导致tlh基因适度去抑制，表明存在一条替代途径将异染色质成分招募到端粒。端粒结合蛋白Taz1可能是这种冗余途径的一部分，tlh转录本在Deltataz1突变体中含量较低，而在Deltataz1 Deltadcr1双突变体中含量较高。令人惊讶的是，含Ago1的RITS复合物的组成成分之一染色质结构域蛋白Chp1对tlh的抑制作用比Ago1更大，这表明Chp1的抑制作用部分独立于RITS。在其他几种真菌的亚端粒区域也发现了tlh基因，这增加了保守调控和功能的有趣可能性。
