Rehman Muhammad Attiq, Wang Dongliang, Fourel Genevieve, Gilson Eric, Yankulov Krassimir
Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario N1G2W1, Canada.
Mol Biol Cell. 2009 Jan;20(2):631-41. doi: 10.1091/mbc.e08-01-0099. Epub 2008 Nov 12.
Subtelomeric genes are either fully active or completely repressed and can switch their state about once per 20 generations. This meta-stable telomeric position effect is mediated by strong repression signals emitted by the telomere and relayed/enhanced by weaker repressor elements called proto-silencers. In addition, subtelomeric regions contain sequences with chromatin partitioning and antisilencing activities referred to as subtelomeric antisilencing regions. Using extensive mutational analysis of subtelomeric elements, we show that ARS consensus sequence (ACS)-containing proto-silencers convert to antisilencers in several replication factor mutants. We point out the significance of the B1 auxiliary sequence next to ACS in mediating these effects. In contrast, an origin-derived ACS does not convert to antisilencer in mutants and its B1 element has little bearing on silencing. These results are specific for the analyzed ACS and in addition to the effects of each mutation (relative to wild type) on global silencing. Another line of experiments shows that Mcm5p possesses antisilencing activity and is recruited to telomeres in an ACS-dependent manner. Mcm5p persists at this location at the late stages of S phase. We propose that telomeric ACS are not static proto-silencers but conduct finely tuned silencing and antisilencing activities mediated by ACS-bound factors.
亚端粒基因要么完全活跃，要么完全被抑制，并且大约每20代就会切换一次状态。这种亚稳态的端粒位置效应由端粒发出的强抑制信号介导，并由称为原沉默子的较弱抑制元件传递/增强。此外，亚端粒区域包含具有染色质分配和抗沉默活性的序列，称为亚端粒抗沉默区域。通过对亚端粒元件进行广泛的突变分析，我们发现含有ARS共有序列（ACS）的原沉默子在几个复制因子突变体中会转变为抗沉默子。我们指出了ACS旁边的B1辅助序列在介导这些效应中的重要性。相比之下，源自起源的ACS在突变体中不会转变为抗沉默子，并且其B1元件对沉默几乎没有影响。这些结果对于所分析的ACS是特异性的，并且除了每个突变（相对于野生型）对全局沉默的影响之外。另一系列实验表明，Mcm5p具有抗沉默活性，并以ACS依赖的方式被招募到端粒。Mcm5p在S期后期持续存在于该位置。我们提出，端粒ACS不是静态的原沉默子，而是由与ACS结合的因子介导进行精细调节的沉默和抗沉默活动。
