论文标题
MAPT基因在进行性上核瘫痪大脑中被差异化
The MAPT gene is differentially methylated in the progressive supranuclear palsy brain
论文作者
论文摘要
背景：进行性核上麻痹（PSP）是一种罕见的神经退行性疾病，导致帕金森氏症状。微管相关蛋白tau基因的DNA甲基化改变与阿尔茨海默氏病和帕金森氏病大脑的表达变化相关。然而，很少有研究检查构成启动子以外的序列。目标：由于通过甲基化激活不同的微管相关的蛋白质tau基因控制区域可能调节构成单个tauopanty的特定特异性的差异tau表达，因此我们比较了候选启动子的甲基化，inthods inton dna 5 n.methods：我们评估了dna甲基化患者的甲基化患者。阿尔茨海默氏病，10个皮质性变性和18个PSP）和19个对照，内含子0 pyrosequencing。我们还评估了11个PSP病例和12个对照组的独立队列中的甲基化。分析额叶（受tau病理学）和枕骨（未受影响）皮质的影响。分析：在初始样品中，与对照相比，内含子0（CPG1）中的一个CpG岛位点（CPG1）中的一个CPG岛位点（CPG1）显示出受PSP影响的额叶皮质的明显低甲基化（P = 0.022）。在复制样品中观察到这种低甲基化，但在枕叶或其他tauopathies中观察到。调整潜在混杂因子（年龄，H1/H1外交类型； P = 0.0005）后，PSP和对照样品（结合初始样品和重复样品组合）保持显着差异。 PSP-affected tissues exhibited microtubule-associated protein tau RNA hyperexpression when compared with controls (p = 0.004), although no correlation with CpG1 methylation was observed.Conclusions: This exploratory study suggests that regions other than the constitutive promoter may be involved in microtubule-associated protein tau gene regulation in tauopathies and that intron 0 hypomethylation may成为PSP的特定表观遗传特征。这些初步发现需要确认。
Background: Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease causing parkinsonian symptoms. Altered DNA methylation of the microtubule-associated protein tau gene correlates with the expression changes in Alzheimer's disease and Parkinson's disease brains. However, few studies examine the sequences beyond the constitutive promoter.Objectives: Because activating different microtubule associated protein tau gene control regions via methylation might regulate the differential tau expression constituting the specific signatures of individual tauopathies, we compared methylation of a candidate promoter, intron 0.Methods: We assessed DNA methylation in the brains of patients with different tauopathies (35 Alzheimer's disease, 10 corticobasal degeneration, and 18 PSP) and 19 controls by intron 0 pyrosequencing. We also evaluated methylation in an independent cohort of 11 PSP cases and 12 controls. Frontal (affected by tau pathology) and occipital (unaffected) cortices were analyzed.Results: In the initial samples, one CpG island site in intron 0 (CpG1) showed significant hypomethylation in PSP-affected frontal cortices when compared with controls (p = 0.022). Such hypomethylation was observed in replicate samples, but not in occipital cortices or other tauopathies. PSP and control samples (combining the initial and replicate samples) remained significantly different after adjustment for potential confounding factors (age, H1/H1 diplotype; p = 0.0005). PSP-affected tissues exhibited microtubule-associated protein tau RNA hyperexpression when compared with controls (p = 0.004), although no correlation with CpG1 methylation was observed.Conclusions: This exploratory study suggests that regions other than the constitutive promoter may be involved in microtubule-associated protein tau gene regulation in tauopathies and that intron 0 hypomethylation may be a specific epigenetic signature of PSP. These preliminary findings require confirmation.
