Reversible chemical modifications on nucleic acids and proteins determine cell fates.The five bases that comprise nucleic acids-adenine,guanine,cytosine,thymine,and uracil-can be chemically and enzymatically modified.These chemical events can have significant biological consequences,particularly for gene expression,and affect various human diseases.I will present chemical strategies we have developed to study newly discovered nucleic acid modifications such as 5-hydroxymethylcytosine(5hmC),5-formylcytosine(5fC),and 5-carboxylcytosine(5caC) that play epigenetic roles in mammalian cells and impact stem cell differentiation and cancer proliferation.