Reduction with age in methylcytosine in the promoter region-224 ∼-101 of the amyloid precursor protein gene in autopsy human cortex
Reduction with age in methylcytosine in the promoter region-224 ∼-101 of the amyloid precursor protein gene in autopsy human cortex
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DOI：
10.1016/s0169-328x(99)00163-1
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发表时间：
1999-07-05
期刊：
影响因子：
--
通讯作者：
Ukitsu, M
中科院分区：
文献类型：
--
作者：
Tohgi, H;Utsugisawa, K;Ukitsu, M
应用亚硫酸氢盐基因组测序技术，分析了人尸检大脑皮质淀粉样前体蛋白（APP）启动子区（-226与-101相似）胞嘧啶甲基化状态及其随年龄的变化。在13个位置的胞嘧啶甲基化的情况下，至少有一个研究。小于或等于70岁的病例（26%）比>70岁的病例（8%）在这些部位的甲基胞嘧啶更常见（p < 0.05）。-207、-204、-200和-182位的胞嘧啶经常被甲基化，170岁的病例中甲基胞嘧啶的频率（55%）显著高于> 70岁的病例（5%）（p < 0.01）。这些胞嘧啶构成了一个9 bp长的GC富集元件（GGGCGC G/A GG）或一个11 bp的嵌入重复序列（GGCCGT CGGCC）。目前的研究结果表明，一些胞嘧啶，特别是那些在-207类似于-182，在APP基因的启动子区域经常被甲基化，并建议他们的去甲基化随着年龄的增长可能有一些意义的AP沉积在老年脑的发展。这些元件在APP基因的总启动子活性中的相对重要性仍有待确定。(C)1999 Elsevier Science B. V.保留所有权利。
Methylation status of cytosines and its changes with age in the promoter region (-226 similar to -101) of the amyloid precursor protein (APP) was analyzed using bisulfite genomic sequencing in the cerebral cortex of human autopsy brain. Cytosines at 13 locations were methylated in at least one of the cases studied. Methylcytosines at these locations was more frequent in cases less than or equal to 70 years old (26%) than in cases >70 years old (8%) (p < 0.05). Cytosines at -207, -204, -200, and -182 are frequently methylated, and the frequency of methylcytosine in these locations was significantly higher in cases 170 years old (55%) than cases > 70 years old (5%) (p < 0.01). These cytosines constituted one of the 9-bp-long GC-rich elements (GGGCGC G/A GG) or an Il-bp invested repeat (GGCCGT CGGCC). The present findings indicate that some cytosines, particularly those at -207 similar to -182, in the promoter region of the APP gene are frequently methylated and suggest that their demethylation with age may have some significance in the development of AP deposition in the aged brain. The relative importance of these elements in the total promoter activity of the APP gene remains to be definitively established. (C) 1999 Elsevier Science B.V. All rights reserved.