– Gaston Jean-Louis ’16

Control of gene expression has long been an area of interest due to its potential as a source of targeted therapies for a range of diseases.  Yet despite the great deal of research that has been conducted in this area, one aspect of gene expression has remained a mystery: does the addition of a methyl (CH) group to certain DNA sequences silence gene expression, or are genes silenced by some other mechanism before being methylated?

The DNA methylation question has gone unresolved for nearly one hundred years, but a recent study conducted in the lab of Daniel G. Tenen of Harvard Medical School and the Harvard Stem Cell Institute offers some answers.  The study presents a newly identified type of functional RNA produced by individual genes during transcription that determines whether a gene is methylated, indicating that methylation in fact enforces gene silencing. The new form of RNA, dubbed “extracoding RNA,” can inhibit an enzyme known as DNA methylase 1 (DNMT1) that carries out the addition of methyl groups to DNA.

The team found unexpectedly that DNMT1, which was previously considered to be a DNA binding protein, can also bind RNA molecules.  When the RNA was shut off, the gene was allowed to become methylated, while adding extracoding RNA to cells prevented DNMT1 from maintaining gene methylation patterns.  This result suggests that extracoding RNA can protect genes from methylation, allowing the genes to be expressed.

Given the importance of gene expression in the development of cancer and other human diseases, this discovery may open a path to more effective therapies.  Tenen points out that while some forms of cancer and other illnesses are already treated with drugs that cause demethylation, this research “gives us the opportunity to try to direct gene-specific demethylation.”

 

More information can be found here.  The original paper, published in Nature, can also be viewed here.

Image credit: Christoph Bock (Max Planck Institute for Informatics)

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