Chips spark surge in epigenetics

Since my colleague Brendan Maher returned from a chromatin meeting in January, it seems there's been a burst of activity in the epigenetics field, much of it covered here in __The Scientist__. On March 17, for instance, I linkurl:reported;http://www.the-scientist.com/news/display/23235/ on the publication of three papers in __Genes & Development__, which mapped the binding of the Dosage Compensation Complex (DCC) across the __Drosophila__ X chromosome during fly development. Today, __linkurl:Nature Genetics;http://www.nature.com/ng/journal/vaop/ncurrent/abs/ng1792.html __and __linkurl:PloS Biology;http://biology.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pbio.0040170 __ released papers that independently map Polycomb group (PcG) proteins across large swaths of the __Drosophila__ genome. Also today, our news site carries a linkurl:story;http://www.the-scientist.com/news/display/23337/ on three papers (in __Cell__ and __Nature__) that map chromatin proteins across the genome in mammalian stem cells, suggesting that PcG complexes may help maintain totipotency in embryonic stem cells. Why the sudden flurry in genome-wide epigenetics research? Probably it's due to the recent availability of high-density tiling microarrays from the likes of Agilent and Nimblegen. Most commonly these are paired with chromatin immunoprecipitation (ChIP), a combination called "ChIP-on-chip". But today's __Nature Genetics__ article uses an alternate method, called DamID. DamID employs a fusion of the chromatin protein with the __Escherichia coli__ Dam methylase to specifically methylate DNA at its binding site. "The idea is that anywhere where your fusion protein binds, this enzyme will put methyl marks on the adenine position, and this leaves a covalent footprint where the protein has been bound," says Maarten van Lohuizen, head of the division of molecular genetics at the Netherlands Cancer Institute and lead author on the __Nature Genetics__ paper. These footprints are then located using restriction enzymes that can differentiate methylated from non-methylated DNA, amplified by PCR, and hybridized to arrays. According to van Lohuizen, ChIP-on-chip and DamID are complementary techniques, each having its own advantages and disadvantages. For instance, while ChIP requires antibodies to the protein of interest, DamID involves expression of a fusion protein in vivo. DamID, on the other hand, is very sensitive, he says, meaning it can be scaled down for use in vivo or with low cell numbers. "This is the future, I think, where we will go with this technique." No doubt new analyses using both techniques are in the pipeline. Meanwhile, for more on advances in epigenetics, see our May issue, which includes a feature from Brendan Maher on efforts to deconstruct the complex web of histone modifications, as well as a look at the development of ChIP, circa 1992.

Chips spark surge in epigenetics

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