In the past few years, researchers have discovered a cyclic pathway by which the DNA base cytosine undergoes methylation and the methylated version is later oxidized and demethylated back to cytosine—modifications that signal genes to turn on and off in cells. Researchers would like to be able to detect, profile, and sequence all four methylated or oxidized cytosine derivatives on the pathway so they can learn more about the functional roles they play in regulating gene expression, cell differentiation, and development. But effective methods for detecting, profiling, and sequencing two of the compounds, 5-formylcytosine and 5-carboxylcytosine, have not been available. Now, Peng Jin of Emory University, Chuan He of the University of Chicago, and coworkers have devised two selective chemical methods for studying 5-formylcytosine (Cell, DOI: 10.1016/j.cell.2013.04.001). The methods—selective biotin labeling and chemically assisted bisulfite sequencing—allowed them to profile 5-formylcytosine’s genomewide distribution and to sequence it with single-base resolution in genomic DNA from mouse embryonic stem cells. The researchers hope to use the techniques to “assess if aberrant demethylation contributes to cancer development and proliferation,” He says.