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Hypomethylation of Intragenic LINE-1 Represses Transcription in Cancer Cells through AGO2

Author

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  • Chatchawit Aporntewan
  • Chureerat Phokaew
  • Jittima Piriyapongsa
  • Chumpol Ngamphiw
  • Chupong Ittiwut
  • Sissades Tongsima
  • Apiwat Mutirangura

Abstract

In human cancers, the methylation of long interspersed nuclear element -1 (LINE-1 or L1) retrotransposons is reduced. This occurs within the context of genome wide hypomethylation, and although it is common, its role is poorly understood. L1s are widely distributed both inside and outside of genes, intragenic and intergenic, respectively. Interestingly, the insertion of active full-length L1 sequences into host gene introns disrupts gene expression. Here, we evaluated if intragenic L1 hypomethylation influences their host gene expression in cancer. First, we extracted data from L1base (http://l1base.molgen.mpg.de), a database containing putatively active L1 insertions, and compared intragenic and intergenic L1 characters. We found that intragenic L1 sequences have been conserved across evolutionary time with respect to transcriptional activity and CpG dinucleotide sites for mammalian DNA methylation. Then, we compared regulated mRNA levels of cells from two different experiments available from Gene Expression Omnibus (GEO), a database repository of high throughput gene expression data, (http://www.ncbi.nlm.nih.gov/geo) by chi-square. The odds ratio of down-regulated genes between demethylated normal bronchial epithelium and lung cancer was high (p

Suggested Citation

  • Chatchawit Aporntewan & Chureerat Phokaew & Jittima Piriyapongsa & Chumpol Ngamphiw & Chupong Ittiwut & Sissades Tongsima & Apiwat Mutirangura, 2011. "Hypomethylation of Intragenic LINE-1 Represses Transcription in Cancer Cells through AGO2," PLOS ONE, Public Library of Science, vol. 6(3), pages 1-13, March.
    • Handle: RePEc:plo:pone00:0017934
    DOI: 10.1371/journal.pone.0017934
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    References listed on IDEAS

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    1. Jeffrey S. Han & Suzanne T. Szak & Jef D. Boeke, 2004. "Transcriptional disruption by the L1 retrotransposon and implications for mammalian transcriptomes," Nature, Nature, vol. 429(6989), pages 268-274, May.
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    1. Federica Rota & Anastasia Conti & Laura Campo & Chiara Favero & Laura Cantone & Valeria Motta & Elisa Polledri & Rosa Mercadante & Giorgio Dieci & Valentina Bollati & Silvia Fustinoni, 2018. "Epigenetic and Transcriptional Modifications in Repetitive Elements in Petrol Station Workers Exposed to Benzene and MTBE," IJERPH, MDPI, vol. 15(4), pages 1-14, April.

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