5-Hydroxymethylcytosine

[5][8] The exact function of this nitrogen base is still not fully elucidated, but it is thought that it may regulate gene expression or prompt DNA demethylation.

This hypothesis is supported by the fact that artificial DNA that contains 5-hydroxymethylcytosines (5hmC) can be converted into unmodified cytosines once introduced into mammalian cells.

[9] Moreover, 5hmC is highly enriched in primordial germ cells, where it apparently plays a role in global DNA demethylation.

[13] The accumulation of 5-hydroxymethylcytosine (5hmC) in post-mitotic neurons is associated with “functional demethylation” that facilitates transcription and gene expression.

“Functional demethylation” refers to the replacement of 5mC by 5hmC, ordinarily a single-step TET-mediated reaction, that also facilitates gene expression, an effect similar to that of “demethylation.” Phages probably evolved to use 5hmC to avoid recognition by most restriction enzymes in bacteria.

[18] This was demonstrated in vitro and in live human and mouse cells by scientists working in the labs of Anjana Rao and David R. Liu.

Yura found 5-hmC present at extremely high levels in rat brain and liver, completely supplanting 5-methylcytosine.

Skeletal formula of 5-hydroxymethylcytosine
Ball-and-stick model of the 5-hydroxymethylcytosine molecule