Trypanosoma brucei expresses Variant Surface Glycoprotein (VSG) genes in a strictly monoallelic fashion in its mammalian hosts, and the regulation of this important virulence mechanism has been the research focus for decades. Telomere position effect (TPE), an epigenetic phenomenon, has been proposed to play a critical role in VSG regulation, yet no telomeric protein was identified whose disruption led to VSG derepression. We recently identified tbRAP1 as an intrinsic component of the T. brucei telomere complex and a major regulator for silencing VSG expression sites (ESs). Knockdown of tbRAP1 led to derepression of all ES-linked VSGs but not VSGs located elsewhere, and resulted in stronger derepression of telomere-proximal genes than telomere-distal genes. This tapered silencing pattern further argues that telomere integrity plays a key role in tbRAP1-dependent silencing and for the first time provides direct evidence indicating that telomeres are important for VSG expression regulation. Whether chromatin remodeling is important for tbRAP1-mediated silencing as in classical TPE will also be discussed.

中文翻译：

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新发现的端粒在古代生物中的作用

布氏锥虫在其哺乳动物宿主中以严格的单等位基因方式表达变异表面糖蛋白 (VSG) 基因，几十年来，这种重要毒力机制的调控一直是研究的重点。端粒位置效应 (TPE) 是一种表观遗传现象，已被提议在 VSG 调节中发挥关键作用，但尚未发现端粒蛋白的破坏导致 VSG 去抑制。我们最近将 tbRAP1 确定为布氏锥虫端粒复合体的内在成分和沉默 VSG 表达位点 (ES) 的主要调节剂。tbRAP1 的敲除导致所有与 ES 相关的 VSG 的去抑制，但不是位于其他地方的 VSG，并且导致端粒近端基因的去抑制比端粒远端基因更强。这种逐渐变细的沉默模式进一步表明端粒完整性在 tbRAP1 依赖性沉默中起着关键作用，并首次提供直接证据表明端粒对 VSG 表达调控很重要。还将讨论染色质重塑是否对 tbRAP1 介导的沉默很重要，如在经典 TPE 中。