Vasiljeva Lidia, Kim Minkyu, Terzi Nihal, Soares Luis M, Buratowski Stephen
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
Mol Cell. 2008 Feb 15;29(3):313-23. doi: 10.1016/j.molcel.2008.01.011.
Within the heterochromatin of budding yeast, RNA polymerase II (RNAPII) transcription is repressed by the Sir2 deacetylase. Although heterochromatic silencing is generally thought to be due to limited accessibility of the underlying DNA, there are several reports of RNAPII and basal transcription factors within silenced regions. Analysis of the rDNA array revealed cryptic RNAPII transcription within the "nontranscribed" spacer region. These transcripts are terminated by the Nrd1/Sen1 complex and degraded by the exosome. Mutations in this pathway lead to decreased silencing and dramatic chromatin changes in the rDNA locus. Interestingly, Nrd1 mutants also show higher levels of rDNA recombination, suggesting that the cryptic RNAPII transcription might have a physiological role in regulating rDNA copy number. The Nrd1/Sen1/exosome pathway also contributes to silencing at telomeric loci. These results suggest that silencing of heterochromatic genes in Saccharomyces cerevisiae occurs at both transcriptional and posttranscriptional levels.
在出芽酵母的异染色质中，RNA聚合酶II（RNAPII）转录受Sir2脱乙酰酶抑制。尽管一般认为异染色质沉默是由于潜在DNA的可及性有限，但有几份报告指出沉默区域内存在RNAPII和基础转录因子。对rDNA阵列的分析揭示了“非转录”间隔区内的隐蔽RNAPII转录。这些转录本由Nrd1/Sen1复合物终止，并由外切体降解。该途径中的突变导致rDNA位点的沉默降低和显著的染色质变化。有趣的是，Nrd1突变体还表现出更高水平的rDNA重组，这表明隐蔽的RNAPII转录可能在调节rDNA拷贝数方面具有生理作用。Nrd1/Sen1/外切体途径也有助于端粒位点的沉默。这些结果表明，酿酒酵母中异染色质基因的沉默发生在转录和转录后水平。
