Institute for Genome Sciences and Policy and Department of Biochemistry, Duke University, Durham, NC 27708, USA.
Genetics. 2010 May;185(1):113-27. doi: 10.1534/genetics.109.113100. Epub 2010 Feb 22.
Heterochromatin is notable for its capacity to propagate along a chromosome. The prevailing model for this spreading process postulates that silencing proteins are first recruited to silencer sequences and then spread from these sites independently of the silencers. However, we found that in Saccharomyces cerevisiae silencers also influence the extent of silenced chromatin domains. We compared the abilities of two different silencers, HMR-E and a telomeric repeat, to promote silencing and found that the HMR-E silencer contributed to an increased steady-state association of Sir proteins over a region of several kilobase pairs compared to the telomeric repeat, even though both silencers recruited similar levels of Sir proteins. We also discovered that, although the HMR-E silencer alone was sufficient to block transcription of the HMR locus, a secondary silencer, HMR-I, boosted the level of Sir proteins at HMR, apparently beyond the level necessary to repress transcription. Finally, we discovered that a tRNA(Thr) gene near HMR-I helped maintain silenced chromatin and transcriptional repression under conditions of reduced deacetylase activity. This study highlights the importance of auxiliary elements, such as HMR-I and the tRNA(Thr) gene, in enhancing the association of Sir silencing proteins with appropriate genomic locations, thereby buffering the capacity of silenced chromatin to assemble under suboptimal conditions.
异染色质的一个显著特点是能够沿着染色体传播。这种扩散过程的主流模型假设沉默蛋白首先被招募到沉默序列,然后独立于沉默序列从这些位点扩散。然而,我们发现酿酒酵母中的沉默子也会影响沉默染色质区域的范围。我们比较了两个不同的沉默子,HMR-E 和端粒重复序列,发现与端粒重复序列相比,HMR-E 沉默子促进了 Sir 蛋白在几个千碱基对的区域中的稳定结合,即使这两个沉默子都招募了相似水平的 Sir 蛋白。我们还发现,尽管 HMR-E 沉默子本身足以阻止 HMR 基因座的转录,但一个次要的沉默子 HMR-I 会增加 HMR 处的 Sir 蛋白水平,显然超过了抑制转录所需的水平。最后,我们发现 HMR-I 附近的 tRNA(Thr)基因有助于在去乙酰化酶活性降低的条件下维持沉默染色质和转录抑制。这项研究强调了辅助元件(如 HMR-I 和 tRNA(Thr)基因)的重要性,这些元件有助于 Sir 沉默蛋白与适当的基因组位置结合,从而缓冲沉默染色质在非最佳条件下组装的能力。