Showing papers on "Nucleolar chromatin published in 2011"

Epigenetic Silencing of Nucleolar rRNA Genes in Alzheimer's Disease

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.

The Structure of rDNA Chromatin

Abstract: The nucleolus is the site of transcription of large tandem repeated arrays of the rDNA which carry the genes for three of the four ribosomal RNAs in eukaryotes. We describe the general genomic features of the rDNA and review what is currently known about its physical organization within the nucleolus. rDNA, like other parts of eukaryotic genomes, is complexed with histones and other proteins to form chromatin, which can adopt at least three functional states that are likely to correlate with physical organization. We review the current state of knowledge of the histones and non-histone proteins in nucleolar chromatin, highlighting both similarities and differences between nucleolar and nuclear chromatin fractions.