Gene Body Methylation can alter Gene Expression and is a Therapeutic Target in Cancer

By Xiaojing Yang, Han F Han, Daniel D. De Carvalho, F. Lay, Peter A. Jones, G. Liang. Cancer Cell, 2014

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SUMMARY DNA methylation in promoters is well known to silence genes and is the presumed therapeutic target of methylation inhibitors. Gene body methylation is positively correlated with expression yet its function is unknown. We show that 5-aza-2'-deoxycytidine treatment not only reactivates genes but decreases the over-expression of genes, many of which are involved in metabolic processes regulated by c-MYC. Down-regulation is caused by DNA demethylation of the gene bodies and restoration of high levels of expression requires remethylation by DNMT3B. Gene body methylation may therefore be an unexpected therapeutic target for DNA methylation inhibitors, resulting in the normalization of gene over-expression induced during carcinogenesis. Our results provide direct evidence for a causal relationship between gene body methylation and transcription.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/1530514247ae79a3ead0e83f0f357cf6146f1ed1