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: U87MG cells cultured in 0.1% O2 demonstrated evidence of HIF-1α protein expression (Fig. S1) by 4 hrs. The cells also showed characteristic signs of apoptosis like cellular shrinkage, nuclear condensation and membrane blebbing in the form of apoptotic bodies even at 6 weeks (Fig. 1A). Similar characteristic changes were also observed in SaOS2 cells. The apoptotic feature of cleaved caspase was also seen in U87MG cell lysates at 1, 2 and 3 days of hypoxia and was found to persist till at least 6 weeks of hypoxic treatment (Fig. 1C).
Affiliation: Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.