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首页> 外文期刊>Nature >DNA triplet repeats mediate heterochromatin-protein-1-sensitive variegated gene silencing
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DNA triplet repeats mediate heterochromatin-protein-1-sensitive variegated gene silencing

机译：DNA三联体重复介导异染色质蛋白-1敏感的杂色基因沉默。

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摘要

Gene repression is crucial to the maintenance of differentiated cell types in multicellular organisms, whereas aberrant silencing can lead to disease. The organization of DNA into chromatin and heterochromatin(1) is implicated in gene silencing. In chromatin, DNA wraps around histones, creating nucleosomes. Further condensation of chromatin, associated with large blocks of repetitive DNA sequences, is known as heterochromatin. Position effect variegation (PEV) occurs when a gene is located abnormally close to heterochromatin, silencing the affected gene in a proportion of cells(1). Here we show that the relatively short triplet-repeat expansions found inmyotonic dystrophy and Friedreich's ataxia confer variegation of expression on a linked transgene in mice. Silencing was correlated with a decrease in promoter accessibility and was enhanced by the classical PEV modifier heterochromatin protein 1 ( HP1). Notably, triplet-repeat-associated variegation was not restricted to classical heterochromatic regions but occurred irrespective of chromosomal location. Because the phenomenon described here shares important features with PEV, the mechanisms underlying heterochromatin-mediated silencing might have a role in gene regulation at many sites throughout the mammalian genome and modulate the extent of gene silencing and hence severity in several triplet-repeat diseases. [References: 30]
机译：基因抑制对于维持多细胞生物中分化的细胞类型至关重要，而异常沉默可能导致疾病。 DNA组成染色质和异染色质（1）的组织与基因沉默有关。在染色质中，DNA包裹组蛋白，形成核小体。与大块重复DNA序列相关的染色质进一步缩合称为异染色质。当基因异常靠近异染色质定位时，就会发生位置效应变异（PEV），从而使受影响的基因在一定比例的细胞中沉默（1）。在这里，我们显示相对短的三联体重复扩增发现肌强直性营养不良和弗里德里希共济失调赋予小鼠连接的转基因表达差异。沉默与启动子可及性的降低相关，并且被经典的PEV修饰剂异染色质蛋白1（HP1）增强。值得注意的是，三联体重复相关的杂色不限于经典的异色区域，而与染色体的位置无关。由于此处描述的现象与PEV具有重要特征，因此异染色质介导的沉默的潜在机制可能在整个哺乳动物基因组的许多位点的基因调控中起作用，并调节基因沉默的程度，从而调节几种三重重复疾病的严重性。 [参考：30]

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