5-hydroxymethylcytosine’s (5-hmC) discovery last year in mammalian DNA (Kriaucionis & Heintz, Science, 2009. and Tahiliani et al., Science, 2009), left the epigenetics community more shaken than a 007 martini. Although its broader role (if any) in epigenetics remains a mystery today, early evidence suggests a few putative mechanisms that could have big implications.
Last year’s discovery of 5-hydroxymethylcytosine (5-hmC) caused some epigenetics researchers to suffer a crisis of confidence, provoking many hours of soul-searching questions such as “are my methylation data really accurate?” and “what if what I thought was gene silencing is really activation?” Although current estimates place 5-hmC levels at only a fraction of the 5-mC content in most cells, it could still be enough to foul up your data interpretation, especially if 5-hmC’s function ends up being antithetical to 5-mC’s as some researchers have proposed.
One of the great things about science is that whenever a new problem presents itself, there are always some members of the community who set out to find innovative solutions. In this case, it’s been a bear to detect and quantify 5-hydroxymethylcytosine (5-hmC) but some cagey researchers at the Ludwig Maximilians University (LMU) in Munich, Germany, have established a simple and accurate method to quantify global levels of genomic 5-hmC.
To say researchers have been pretty amped about 5-Hydroxymethylcytosine (5-hmC) this last year would be an understatement. Is this 6th base for real, or is it some kind of intermediate of it’s more abundant cousin 5-mC? So far its low key presence has been detected in embryonic stem cells, brain, and other organs but there are still far more questions than answers for 5-hmC.
Small pores aren’t just highly sought after in the cosmetics industry. They can really lend a hand in smoothing out the rougher epigenetics experimental challenges researchers face nowadays. Just ask Dr. Meni Wanunu and Marija Drndic at the University of Pennsylvania, along with colleagues from New England Biolabs, Boston University, and Temple University, who put solid-state nanopores to work recently and obtained some glowing DNA methylation profiling results.
A UK team used MeDIP-Seq and hMeDIP-Seq to look at genome-wide patterns of 5mC and 5hmC in mouse ES cells and differentiating embryoid bodies. They found interesting differences in 5mC/5hmC distributions among genomic regions and cell types:
A clever team of researchers has developed two independent approaches for the genome-wide mapping of 5hmC, neither of which relies on 5hmC antibodies.
The team from New England Biolabs and UCLA kicked off their project by developing a method to detect and measure 5-hmC.
Things got even more interesting earlier this year when 5-formylcytosine(5fC) and 5-carboxylcytosine (5caC) was found to be a part of that same pathway. Now, some recent work out Yi Zhang’s lab at the University of North Carolina suggests that 5fC and 5caC appear to be more than just intermediates.
With this and several other methods, they generated detailed genome-wide epigenetic maps of 5-hmC in the mouse cerebellum and hippocampus seven days after birth, at six weeks old, and at one year old leading to lots of new insights into 5-hmC.
