回复 jiabiaohu 的帖子 4 v- O C# h6 X$ K* W& Q% U) F6 _, H
第三篇文章为cell上的。Guo, Junjie U., Y. Su, et al. (2011). "Hydroxylation of 5-Methylcytosine by TET1 Promotes Active DNA Demethylation in the Adult Brain." Cell 145(3): 423-434. . r* D2 V5 T$ `/ Z6 x( u感兴趣的自己下载下来看下吧,我这边上传不了,不知道为什么。作者: tpwang 时间: 2011-5-18 23:25
附件: Hydroxylation of 5-Methylcytosine by TET1 Promotes Active DNA Demethylation in t.pdf (2011-5-18 23:25, 789.44 KB) / 下载次数 21 http://stemcell8.cn/forum.php?mod=attachment&aid=MjcxMTl8ZjBlZmNjZWV8MTcxODU3NTQ0Nnww作者: mcherry.f 时间: 2011-5-18 23:54
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. 3 ^: ~( r: u: K M+ @3 V
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. 作者: jiabiaohu 时间: 2011-5-19 09:21
回复 mcherry.f 的帖子 9 C R/ P- e3 v! b+ v 3 P. d- G+ G4 h% ~+ |1 tFrom the aforementioned article, it seems clear that the demethylation is initiated by Tet1 converting 5mC to 5hmC, following AID deaminate the 5hmC to 5hmU, which is substitued by the C through BER(it is confirmed by inhibiting the enzymes in the BER pathway). & {2 `) `5 G! ~1 c N! t! }. _- x) E; r# I* c% K+ u
The most interesting results of this article I think is integrating the AID and Tet1 to one pathway to demethylate of 5mC. 3 i4 \8 r9 o6 L: j7 u . Z2 S: G9 U9 n- ?( |) pAs reviewed by Zhang Yi, there may be other means for organisms to remove the methylation modification. Anyway, 5mC---5mhC---5mhU---C will be a promising mechanism for demethylation.作者: mcherry.f 时间: 2011-5-19 09:33
回复 jiabiaohu 的帖子 # o0 o( S4 k/ a " [$ @( V" ]6 {+ I- S& [% pYeah, 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. 作者: jiabiaohu 时间: 2011-5-19 10:29
回复 mcherry.f 的帖子 6 N9 p" P. o2 d# G# Q4 r3 R f+ D
Yes, there are still many questions remain elusive in most areas, if not all. We just know a corner of the iceberg of life mestry.作者: zhenhua 时间: 2011-5-19 11:27
在哺乳动物中,发现5hmC的是Anjana Rao lab,他们通过寻找5mC转变成5hmC的酶,发现了哺乳动物中的5hmC。还有另外一个组也发现了。两个工作发在同一期的science上。Anjana Rao 的文章是Conversion of 5-Methylcytosine to 5-Hydroxymethylcytosine in Mammalian DNA by MLL Partner TET1 ! E2 H4 k7 k# h 作者: jiabiaohu 时间: 2011-5-19 19:17