 dna methylation ( 5-methylcytosine , 
 5mc ) plays critical biological 
 functions in mammals and plants as a vital epigenetic marker . 
 the 
 ten - eleven translocation dioxygenases ( tet1 , 2 , and 3 ) have been found 
 to oxidize 5mc to 5-hydroxymethylcytosine ( 5hmc ) and then to 5-formylcytosine 
 ( 5fc ) and 5-carboxylcytosine ( 5cac ) in mammalian cells . 
 we report 
 herein three mushroom tet homologues from coprinopsis cinerea that can mediate 5mc oxidation . 
 specifically , one homologue ( cc1g_05589 , 
 cctet ) shows similar activity to its mammalian tet homologues . 
 biochemically , 
 cctet actively converts 5mc to 5hmc , 5fc , and 5cac under natural conditions 
 ( ph 7.0 ) . 
 interestingly , cctet also converts the majority of 5mc to 
 5fc under slightly acidic ( ph 5.8 ) and neutral conditions . 
 kinetics 
 analyses of the oxidation by cctet under neutral conditions indicate 
 that conversion of 5mc to 5hmc and 5hmc to 5fc are faster than that 
 of 5fc to 5cac , respectively . 
 our results provide an example of a 
 tet homologue in a non - mammalian organism that exhibits full 5mc - to-5cac 
 oxidation activity and a slight preference to producing 5fc . 
 the preferential 
 accumulation of 5fc in the in vitro oxidation reactions 
 under both neutral and acidic conditions may have biological implications 
 for 5mc oxidation in fungi species . 
Supplementary Material