Aberrant methylation and associated transcriptional mobilization of Alu elements contributes to genomic instability in hypoxia.
Bottom Line: Because a majority of the cytosine-phosphate-guanine (CpG) islands are found within the repeat elements of DNA, and are usually methylated under normoxic conditions, we suggested that retrotransposable Alu or short interspersed nuclear elements (SINEs) which show altered methylation and associated changes of gene expression during hypoxia, could be associated with genomic instability.U87MG glioblastoma cells were cultured in 0.1% O₂ for 6 weeks and compared with cells cultured in 21% O₂ for the same duration.Our results show that aberrant methylation leading to increased transcription of SINE and reverse transcriptase associated LINE elements could lead to increased genomic instability in hypoxia.
Affiliation: Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.Show MeSH
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Mentions: From the consensus SINE locus of chromosome 16, 23 CpG sites were chosen for bisulphite PCR sequencing. In U87MG, there was statistically significant decrease in methylation status after exposure to long-term hypoxic conditions which did not change even after reverting back to normoxic conditions. Seventeen sites showed average decrease in methylation by 9.76% (from 91.37% to 81.63%) (P= 0.01) in hypoxia with respect to normoxia (Fig. 3A-i) (Fig. S2). Major hypomethylation was seen at two specific CpG sites (site14: from 91.6% to 47.8% and site17: from 77.1% to 34.2%). Of these two sites, site 17 showed no change in methylation on reversion to normoxia, while at site 14 there was some increase in methylation in revertent (62.8%). The average percentage of methylation of these 17 sites in revertents was 81.5%, i.e. there was almost no change (0.05%) in methylation in comparison to hypoxia (P= 0.97) (Fig. 3A-i).
Affiliation: Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.