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首页> 外文期刊>Epigenetics & Chromatin >Genomic imprinting does not reduce the dosage of UBE3A in neurons
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Genomic imprinting does not reduce the dosage of UBE3A in neurons

机译：基因组印迹不会减少神经元中UBE3A的剂量

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Background The ubiquitin protein E3A ligase gene ( UBE3A ) gene is imprinted with maternal-specific expression in neurons and biallelically expressed in all other cell types. Both loss-of-function and gain-of-function mutations affecting the dosage of UBE3A are associated with several neurodevelopmental syndromes and psychological conditions, suggesting that UBE3A is dosage-sensitive in the brain. The observation that loss of imprinting increases the dosage of UBE3A in brain further suggests that inactivation of the paternal UBE3A allele evolved as a dosage-regulating mechanism. To test this hypothesis, we examined UBE3A transcript and protein levels among cells, tissues, and species with different imprinting states of UBE3A . Results Overall, we found no correlation between the imprinting status and dosage of UBE3A. Importantly, we found that maternal Ube3a protein levels increase in step with decreasing paternal Ube3a protein levels during neurogenesis in mouse, fully compensating for loss of expression of the paternal Ube3a allele in neurons. Conclusions Based on our findings, we propose that imprinting of UBE3A does not function to reduce the dosage of UBE3A in neurons but rather to regulate some other, as yet unknown, aspect of gene expression or protein function.
机译：背景泛素蛋白E3A连接酶基因（UBE3A）基因在神经元中印有母亲特异性表达，并在所有其他细胞类型中双等位表达。影响UBE3A剂量的功能丧失和功能获得突变均与几种神经发育综合征和心理状况有关，这表明UBE3A在大脑中对剂量敏感。印记丢失增加了脑中UBE3A剂量的观察结果进一步表明，父亲UBE3A等位基因的失活是作为剂量调节机制而演变的。为了验证该假设，我们检查了具有不同印迹状态的UBE3A的细胞，组织和物种之间的UBE3A转录本和蛋白质水平。结果总体而言，我们发现印迹状态与UBE3A剂量之间没有相关性。重要的是，我们发现在小鼠神经发生过程中，母体Ube3a蛋白水平随着母体Ube3a蛋白水平的降低而逐步增加，从而完全补偿了神经元中母体Ube3a等位基因表达的损失。结论基于我们的发现，我们建议印记UBE3A的功能不是减少神经元中UBE3A的剂量，而是调节基因表达或蛋白质功能的其他方面（尚不清楚）。

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