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: Real-time PCR and RT-PCR was done with cDNA prepared from total RNA extracted from cells cultured in hypoxia, normoxia and hypoxia of 6 weeks reverted to 4-week normoxia. Average values of two biological replicates are shown. After 6-week hypoxia, there was a 9.57-fold increase in relative expression of SINE in U87MG cells as compared to normoxia (P= 0.0008). In case of SaOS2 the increase in the expression level is approximately 6.30-fold in hypoxia (P= 0.0004). SINE transcripts levels increased only by 1.29-fold in U87MG and 1.36-fold in SaOS2 revertents (Fig. 2A).
Affiliation: Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.