哺乳动物中Active DNA Demethylation机制

mcherry.f

Mammalian DNA demethylation is a long term interest for the scientists in this area for many years. And many results are controversial, so someone dubbed it as "a colorful history". For the AID, it is really a star-molecule since its identification in 2000 around by Japanese. It is the molecule, searched by nearly half a century, responsible for the immunoglobulin somatic hypermutation (SHM). It is really intriguing to find its role in DNA demethylation. Actually, considering the studies presented recently, the mechanism of AID in DNA demethylation is a deamination process  from 5meC to T, and then the T is converted to C again by DNA repair (which repair machinery? MMR or BER or others?). The similar mechanism for somatic hypermutation has been revealed, but for the last step, there is no correct DNA repair, which can introduce mutations in the end. So a very interesting question is what is difference between SHM and DNA demethylation when AID plays its role. As I concerned, the level of AID may be the key, because SHM only occurs in B cells, which has high expression level of AID. But for ESCs, the transcriptome data indicates that its level is far less than in B cells. $ u! s" M" q; j7 a
For reprogramming, AID is just to diminish the protection of DNA (methylation state makes many genes inactive), while other pluripotent factors function to reprogram the somatic cell into pluripotent one.  

mcherry.f

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Yeah, hydroxylation is essential for 5meC further modification. After there is a base mismatch, why the cell chooses BER instead of MMR is also interesting, because we have already know that MMR will introduce mutations for Ig genes. So the regulation mechanism must be further addressed.