Hdl Handle:
http://hdl.handle.net/10675.2/667
Title:
Epigenetic Silencing of Nucleolar rRNA Genes in Alzheimer's Disease
Authors:
Pietrzak, Maciej; Rempala, Grzegorz A.; Nelson, Peter T.; Zheng, Jing-Juan; Hetman, Michal
Abstract:
Background: 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.; Methodology/Principal Findings: 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.; Conclusions/Significance: 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.
Citation:
PLoS One. 2011 Jul 22; 6(7):e22585
Issue Date:
22-Jul-2011
URI:
http://hdl.handle.net/10675.2/667
DOI:
10.1371/journal.pone.0022585
PubMed ID:
21799908
PubMed Central ID:
PMC3142181
Type:
Article
ISSN:
1932-6203
Appears in Collections:
Department of Biostatistics and Epidemiology: Faculty Research and Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorPietrzak, Maciejen_US
dc.contributor.authorRempala, Grzegorz A.en_US
dc.contributor.authorNelson, Peter T.en_US
dc.contributor.authorZheng, Jing-Juanen_US
dc.contributor.authorHetman, Michalen_US
dc.date.accessioned2012-10-26T16:29:27Zen
dc.date.available2012-10-26T16:29:27Zen
dc.date.issued2011-07-22en_US
dc.identifier.citationPLoS One. 2011 Jul 22; 6(7):e22585en_US
dc.identifier.issn1932-6203en_US
dc.identifier.pmid21799908en_US
dc.identifier.doi10.1371/journal.pone.0022585en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/667en
dc.description.abstractBackground: 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.en_US
dc.description.abstractMethodology/Principal Findings: 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.en_US
dc.description.abstractConclusions/Significance: 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.en_US
dc.rightsPietrzak et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.subjectResearch Articleen_US
dc.subjectBiologyen_US
dc.subjectMolecular Cell Biologyen_US
dc.subjectCellular Structuresen_US
dc.subjectNucleolusen_US
dc.subjectGene Expressionen_US
dc.subjectDNA modificationen_US
dc.subjectNeuroscienceen_US
dc.subjectNeurobiology of Disease and Regenerationen_US
dc.subjectMedicineen_US
dc.subjectNeurologyen_US
dc.subjectDementiaen_US
dc.subjectAlzheimer Diseaseen_US
dc.titleEpigenetic Silencing of Nucleolar rRNA Genes in Alzheimer's Diseaseen_US
dc.typeArticleen_US
dc.identifier.pmcidPMC3142181en_US
dc.contributor.corporatenameDepartment of Biostatistics and Epidemiologyen

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