Institut Curie, Paris, F-75248 France.
Genes Dev. 2011 Jul 1;25(13):1365-70. doi: 10.1101/gad.611011.
The heterochromatin-like structure formed by the yeast silent information regulator complex (SIR) represses transcription at the silent mating type loci and telomeres. Here, we report that tight protein-DNA complexes induce ectopic recruitment of the SIR complex, promoting gene silencing and changes in subnuclear localization when cis-acting elements are nearby. Importantly, lack of the replication fork-associated helicase Rrm3 enhances this induced gene repression. Additionally, Sir3 and Sir4 are enriched genome-wide at natural replication pause sites, including tRNA genes. Consistently, inserting a tRNA gene promotes SIR-mediated silencing of a nearby gene. These results reveal that replication stress arising from tight DNA-protein interactions favors heterochromatin formation.
酵母沉默信息调节复合物（SIR）形成的异染色质样结构可抑制沉默交配型基因座和端粒的转录。在这里，我们报告说，紧密的蛋白质-DNA 复合物诱导 SIR 复合物的异位募集，促进基因沉默，并在顺式作用元件附近时改变亚核定位。重要的是，缺乏与复制叉相关的解旋酶 Rrm3 会增强这种诱导的基因抑制。此外，Sir3 和 Sir4 在自然复制暂停位点（包括 tRNA 基因）的全基因组范围内富集。一致地，插入一个 tRNA 基因可促进 SIR 介导的附近基因沉默。这些结果表明，来自紧密的 DNA-蛋白质相互作用的复制压力有利于异染色质的形成。
