Author(s): Pirazzini C, Giuliani C, Bacalini MG, Boattini A, Capri M,
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Abstract Little is known about the impact of space (geography/ancestry) and time (age of the individuals) on DNA methylation variability in humans. We investigated DNA methylation of the imprinted IGF2/H19 locus in: i) a cohort of individuals homogeneous for age and gender (males with restricted age range: 30-50 years) belonging to four Italian districts representative of the major genetic clines, informative for the geographical dimension; ii) a cohort of monozygotic (MZ) and dizygotic (DZ) twins of different ages (age-range: 22-97 years), informative for the temporal dimension. DNA methylation of the analyzed regions displayed high levels of inter-individual variability that could not be ascribed to any geographical cline. In MZ twins we identified two IGF2/H19 regions where the intra-couple variations significantly increased after the age of 60 years. The analysis of twins' individual life histories suggests that the within twin pairs difference is likely the result of the aging process itself, as sharing a common environment for long periods had no effect on DNA methylation divergence. On the whole, the data here reported suggest that: i) aging more than population genetics is responsible for the inter-individual variability in DNA methylation patterns in humans; ii) DNA methylation variability appears to be highly region-specific.
This article was published in Aging (Albany NY)
and referenced in Journal of Molecular and Genetic Medicine
- Eugene Stephane Mananga
On Fer and Floquet-Magnus expansions: Application in solid-state nuclear magnetic resonance and physics
- Yosef Yarden
Classically, the 3âuntranslated region (3âUTR) is that region in eukaryotic protein-coding genes from the translation termination codon to the polyA signal. It is transcribed as an integral part of the mRNA encoded by the gene. However, there exists another kind of RNA, which consists of the 3âUTR alone, without all other elements in mRNA such as 5âUTR and coding region. The importance of independent 3âUTR RNA (referred as I3âUTR) was prompted by results of artificially introducing such RNA species into malignant mammalian cells. Since 1991, we found that the middle part of the 3âUTR of the human nuclear factor for interleukin-6 (NF-IL6) or C/EBP gene exerted tumor suppression effect in vivo. Our subsequent studies showed that transfection of C/EBP 3âUTR led to down-regulation of several genes favorable for malignancy and to up-regulation of some genes favorable for phenotypic reversion. Also, it was shown that the sequences near the termini of the C/EBP 3âUTR were important for its tumor suppression activity. Then, the C/EBP 3âUTR was found to directly inhibit the phosphorylation activity of protein kinase CPKC in SMMC-7721, a hepatocarcinoma cell line. Recently, an AU-rich region in the C/EBP 3âUTR was found also to be responsible for its tumor suppression. Recently we have also found evidence that the independent C/EBP 3âUTR RNA is actually exists in human tissues, such as fetal liver and heart, pregnant uterus, senescent fibroblasts etc. Through 1990âs to 2000âs, world scientists found several 3âUTR RNAs that functioned as artificial independent RNAs in cancer cells and resulted in tumor suppression. Interestingly, majority of genes for these RNAs have promoter-like structures in their 3âUTR regions, although the existence of their transcribed products as independent 3âUTR RNAs is still to be confirmed. Our studies indicate that the independent 3âUTR RNA is a novel non-coding RNA species whose function should be the regulation not of the expression of their original mRNA, but of some essential life activities of the cell as a whole.
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