Epigenetic silencing of nucleolar rRNA genes in Alzheimer's disease.
Epigenetic silencing of nucleolar rRNA genes in Alzheimer's disease.
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DOI：
10.1371/journal.pone.0022585
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Hetman M
中科院分区：
文献类型：
--
作者：
Pietrzak M;Rempala G;Nelson PT;Zheng JJ;Hetman M
核糖体缺陷记录在轻度认知障碍（MCI）中，其通常代表早期阿尔茨海默病（AD）以及晚期AD。核仁rRNA基因（rDNA）的转录是核糖体生物合成的关键，受表观遗传沉默（包括启动子CpG甲基化）的调控。为了评估rDNA启动子的CpG甲基化是否在整个AD谱中失调，我们使用亚硫酸氢盐作图分析了来自10名MCI-，23名AD-和24名年龄匹配的对照个体的脑样本。在MCI和AD组的大脑皮层样本中，rDNA启动子变得高度甲基化。在顶叶皮层，MCI组rDNA启动子的甲基化程度高于AD组。总基因组DNA的胞嘧啶甲基化在AD、MCI和对照样品中是相似的。与核仁染色质的高甲基化介导的沉默稳定rDNA位点，防止其衰老相关的损失的概念相一致，基因组rDNA含量在MCI和AD组的大脑皮层样品中升高。因此，rDNA高甲基化可能是AD的一个新的表观遗传学标志。此外，核仁染色质的沉默可能发生在AD病理学的早期阶段，并在AD相关的核糖体缺陷中发挥作用，最终导致痴呆。
Ribosomal deficits are documented in mild cognitive impairment (MCI), which often represents an early stage Alzheimer's disease (AD), as well as in advanced AD. The nucleolar rRNA genes (rDNA), transcription of which is critical for ribosomal biogenesis, are regulated by epigenetic silencing including promoter CpG methylation. To assess whether CpG methylation of the rDNA promoter was dysregulated across the AD spectrum, we analyzed brain samples from 10 MCI-, 23 AD-, and, 24 age-matched control individuals using bisulfite mapping. The rDNA promoter became hypermethylated in cerebro-cortical samples from MCI and AD groups. In parietal cortex, the rDNA promoter was hypermethylated more in MCI than in advanced AD. The cytosine methylation of total genomic DNA was similar in AD, MCI, and control samples. Consistent with a notion that hypermethylation-mediated silencing of the nucleolar chromatin stabilizes rDNA loci, preventing their senescence-associated loss, genomic rDNA content was elevated in cerebrocortical samples from MCI and AD groups. In conclusion, rDNA hypermethylation could be a new epigenetic marker of AD. Moreover, silencing of nucleolar chromatin may occur during early stages of AD pathology and play a role in AD-related ribosomal deficits and, ultimately, dementia.
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影响因子：
3.7
作者：
Santoro R;Lienemann P;Fussenegger M
通讯作者：
Fussenegger M
DOI：
10.1523/jneurosci.1064-09.2009
发表时间：
2009-10-14
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Abdul HM;Sama MA;Furman JL;Mathis DM;Beckett TL;Weidner AM;Patel ES;Baig I;Murphy MP;LeVine H 3rd;Kraner SD;Norris CM
通讯作者：
Norris CM
DOI：
10.1097/nen.0b013e31815c5efb
发表时间：
2007-12-01
影响因子：
3.2
作者：
Nelson, Peter T.;Jicha, Gregory A.;Markesbery, William R.
通讯作者：
Markesbery, William R.
影响因子：
5.3
作者：
Parlato, Rosanna;Kreiner, Grzegorz;Schuetz, Guenther
通讯作者：
Schuetz, Guenther
影响因子：
11.4
作者：
Guetg, Claudio;Lienemann, Philipp;Santoro, Raffaella
通讯作者：
Santoro, Raffaella