Friday, April 17, 2009

A new kind of methylation

By now we're all aware of epigenetics and the role of cytosine methylation in gene expression, imprinting and retrotransposon silencing. We may however, have been fooling ourselves, since there may exist another type of methylated cytosine: 5-hydroxymethylcytosine. The journal Science will unveil 2 papers next week describing this novel modification. How could we have missed it for so long? :

"The reason that this nucleotide had not been seen before, the researchers say, is because of the methodologies used in most epigenetic experiments. Typically, scientists use a procedure called bisulfite sequencing to identify the sites of DNA methylation. But this test cannot distinguish between 5-hydroxymethylcytosine and 5-methylcytosine, a shortcoming that has kept the newly discovered nucleotide hidden for years, the researchers say. Its discovery may force investigators to revisit earlier work. The Human Epigenome Project, for example, is in the process of mapping all of the sites of methylation using bisulfite sequencing. "If it turns out in the future that (5-hydroxymethylcytosine and 5-methylcytosine) have different stable biological meanings, which we believe very likely, then epigenome mapping experiments will have to be repeated with the help of new tools that would distinguish the two," says Kriaucionis."

This is exciting, can't wait to read up on it. It seems very abundant, stable and well conserved too...


rob said...

"..have different stable biological meanings, which we believe very likely,.."They don't even know if it has any biological significance and it's two science papers! I guess we think we know DNA pretty well.
Wouldn't the human epigenome project, in trying to make sense of thier data, be running into fairly serious issues if these modifications had massively different effects.
Pretty exciting breakthrough perhaps.

Kamel said...

Larry has a different take on this breakthrough, and points out that this particular modification was discovered in mammals almost 40 years ago.

Still, it's barely been touched since then so it will be interesting to see what these new papers have to say and if they shed some light on this modification's biological function.

It's kind of strange that 5-hydroxymethylcytosine has made almost no appearance in the literature (with regards to animals) considering that 1972 paper claimed it accounts for around 15% of total cytosine bases in certain rat tissues. Could it not be replicated until now?

Bayman said...

More Science-worthy seems the second paper we're not really discussing here:
Conversion of 5-Methylcytosine to 5-Hydroxymethylcytosine in Mammalian DNA by the MLL Fusion Partner TET1
Perhaps a case of the other paper riding the coat-tails a bit to make a back-to-back issue for the editors.