What is the cycle of DNA demethylation?

The cycle of active DNA demethylation begins with the presence of methylated cytosine (5mC) and finishes with the conversion to an unmodified cytosine (C). Initially, 5mC is oxidized to form 5-hydroxymethylcytosine (5hmC), which undergoes further oxidation to produce 5-formylcytosine (5fC). Subsequently, 5fC is oxidized once more to generate 5-carboxylcytosine (5caC). These successive oxidation steps ultimately lead to the removal of the methyl group and the restoration of an unmodified cytosine base. 

During cell division, Dnmt1 functions as a key enzyme to maintain methylation patterns. Its role is to ensure these patterns are accurately copied onto newly synthesized DNA strands. Without properly functioning or inhibited DNMT1/UHRF1, each DNA replication cycle progressively weakens the overall 5mC signal due to un-maintained methylation patterns (resulting in unmethylated cytosines). This weakening can be caused by cofactors hindering the enzyme's ability to access DNA or histone marks which don't permit enzymes to bind to DNA. The progressive accumulation of unmethylated cytosines with each cell division leads to a decline in the overall methylation level. This process is known as passive DNA demethylation.