Hereditary Genetics: Current Research

Transcriptional overlap links DNA hypo-methylation and hyper-methylation of contiguous promoters in cancer

4^th International Congress on Epigenetics & Chromatin

September 03-05, 2018 | London, UK

Charles De Smet

De Duve Institute–University of Louvain, Belgium

Keynote: Hereditary Genet Curr Res

Abstract:

DNA methylation is an epigenetic mark associated with gene repression. It is now well established that alterations in DNA methylation patterns contribute to tumor development. Both gains (hyper-methylation) and losses (hypo-methylation) of DNA methylation marks are frequently observed in tumors. The mechanisms underlying these two are opposite, yet co-existing, alterations in tumors remain, however unclear. Our recent work reveals an unsuspected connection between DNA hypo- and hypermethylation in tumors. We show indeed that DNA hypo-methylation in tumors can lead to the activation of long non-coding transcripts that overlap downstream promoters and trigger their hyper-methylation. Promoters that have gone through this process of hyper-methylation are characterized by an enrichment of H3K36me3, a histone mark known to be deposited during progression of the transcription machinery and to attract DNMT3A/B DNA methyltransferases. Finally, we show that this process of inter dependent epigenetic alteration contributes to the repression of a tumor suppressor gene, RERG, in non-small cell lung carcinomas. Recent Publications 1. Van Tongelen A, Loriot A and De Smet C (2017) Oncogenic roles of DNA hypomethylation through the activation of cancer-germline genes. Cancer Letters 396:130-137. 2. Cannuyer J, Van Tongelen A, Loriot A and De Smet C (2015) A gene expression signature identifying transient DNMT1 depletion as a causal factor of cancer-germline gene activation in melanoma. Clinical Epigenetics 7:114. 3. Loriot A, Van Tongelen A, Blanco J, Klaessens S et al. (2014) A novel cancer-germline transcript carrying prometastatic miR-105 and TET-targeting miR-767 induced by DNA hypomethylation in tumors. Epigenetics 9(8):1163-1171. 4. Cannuyer J, Loriot A, Parvizi K G and De Smet C (2013) Epigenetic hierarchy within the MAGEA1 cancer-germline gene: promoter DNA methylation directs local histone modifications. PLoS ONE, 8(3):e58743. 5. De Smet C and Loriot A (2010) DNA hypomethylation in cancer: epigenetic scars of a neoplastic journey. Epigenetics 5(3):206-

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