Аннотация
Methylation of the cytosine is the most frequent epigenetic modification
of DNA in mammalian cells. In humans, most of the methylated cytosines
are found in CpG-rich sequences within tandem and interspersed repeats
that make up to 45% of the human genome, being Alu repeats the most
common family. Demethylation of Alu elements occurs in aging and
cancer processes and has been associated with gene reactivation and
genomic instability. By targeting the unmethylated SmaI site within
the Alu sequence as a surrogate marker, we have quantified and identified
unmethylated Alu elements on the genomic scale. Normal colon epithelial
cells contain in average 25 486 +/- 10 157 unmethylated Alu's per
haploid genome, while in tumor cells this figure is 41 995 +/- 17
187 (P = 0.004). There is an inverse relationship in Alu families
with respect to their age and methylation status: the youngest elements
exhibit the highest prevalence of the SmaI site (AluY: 42%; AluS:
18%, AluJ: 5%) but the lower rates of unmethylation (AluY: 1.65%;
AluS: 3.1%, AluJ: 12%). Data are consistent with a stronger silencing
pressure on the youngest repetitive elements, which are closer to
genes. Further insights into the functional implications of atypical
unmethylation states in Alu elements will surely contribute to decipher
genomic organization and gene regulation in complex organisms.
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