标题: HHMI Prof. Zhang Yi's recent publication on DNA methylation and demethylation [打印本页] 作者: lixiaodong 时间: 2010-8-11 13:16 标题: HHMI Prof. Zhang Yi's recent publication on DNA methylation and demethylation
Prof. Zhang Yi is a big expert in the epigenetics field.& o2 U6 t+ `" y5 e0 Q- d. ~/ }
Hope those papers are useful.[attach]12055[/attach][attach]12056[/attach][attach]12057[/attach]作者: tspaulzhao 时间: 2010-8-11 23:23
Thank u for sharing so good papers.作者: tspaulzhao 时间: 2010-8-11 23:23
Thank u for sharing so good papers.作者: lixiaodong 时间: 2010-8-12 12:22
附上Abstrat： ' g9 D7 x1 ~& b/ w+ ?& `. F, u0 cZhangY-elongator.pdf： ) p- A! K! P/ k% C% i: u/ k3 V1 bNature. 2010 Jan 28;463(7280):554-8. Epub 2010 Jan 6. u0 x6 W9 [1 ?/ }
A role for the elongator complex in zygotic paternal genome demethylation. 5 T9 P; U& J2 ?, y2 o( w0 FOkada Y, Yamagata K, Hong K, Wakayama T, Zhang Y.$ O& F4 c' E: B& f0 k' `
Howard Hughes Medical Institute, Chapel Hill, North Carolina 27599-7295, USA.# D, D5 e0 q# Z& X! X
Abstract6 J6 J/ q8 I$ a+ j
The life cycle of mammals begins when a sperm enters an egg. Immediately after fertilization, both the maternal and paternal genomes undergo dramatic reprogramming to prepare for the transition from germ cell to somatic cell transcription programs. One of the molecular events that takes place during this transition is the demethylation of the paternal genome. Despite extensive efforts, the factors responsible for paternal DNA demethylation have not been identified. To search for such factors, we developed a live cell imaging system that allows us to monitor the paternal DNA methylation state in zygotes. Through short-interfering-RNA-mediated knockdown in mouse zygotes, we identified Elp3 (also called KAT9), a component of the elongator complex, to be important for paternal DNA demethylation. We demonstrate that knockdown of Elp3 impairs paternal DNA demethylation as indicated by reporter binding, immunostaining and bisulphite sequencing. Similar results were also obtained when other elongator components, Elp1 and Elp4, were knocked down. Importantly, injection of messenger RNA encoding the Elp3 radical SAM domain mutant, but not the HAT domain mutant, into MII oocytes before fertilization also impaired paternal DNA demethylation, indicating that the SAM radical domain is involved in the demethylation process. Our study not only establishes a critical role for the elongator complex in zygotic paternal genome demethylation, but also indicates that the demethylation process may be mediated through a reaction that requires an intact radical SAM domain.0 J8 ]( L' p1 }+ Y
PMID: 20054296 [PubMed - indexed for MEDLINE]PMCID: PMC2834414Free作者: lixiaodong 时间: 2010-8-12 12:26
ZhangY-Tet1.pdf1 c, q' g N2 b$ I/ w5 h
Nature. 2010 Jul 18. [Epub ahead of print]6 s1 x! L2 f/ f- ^6 {4 T
Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification. 0 K" Z2 P% Y4 j7 p8 x0 pIto S, D'Alessio AC, Taranova OV, Hong K, Sowers LC, Zhang Y.* ]( Q) t: Z* X& Y6 J. L
[1] Howard Hughes Medical Institute, [2] Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7295, USA.8 \ w! G( R% M& y2 E$ Y
Abstract* P2 l7 N! F" C4 H$ t* I
DNA methylation is one of the best-characterized epigenetic modifications. Although the enzymes that catalyse DNA methylation have been characterized, enzymes responsible for demethylation have been elusive. A recent study indicates that the human TET1 protein could catalyse the conversion of 5-methylcytosine (5mC) of DNA to 5-hydroxymethylcytosine (5hmC), raising the possibility that DNA demethylation may be a Tet1-mediated process. Here we extend this study by demonstrating that all three mouse Tet proteins (Tet1, Tet2 and Tet3) can also catalyse a similar reaction. Tet1 has an important role in mouse embryonic stem (ES) cell maintenance through maintaining the expression of Nanog in ES cells. Downregulation of Nanog via Tet1 knockdown correlates with methylation of the Nanog promoter, supporting a role for Tet1 in regulating DNA methylation status. Furthermore, knockdown of Tet1 in pre-implantation embryos results in a bias towards trophectoderm differentiation. Thus, our studies not only uncover the enzymatic activity of the Tet proteins, but also demonstrate a role for Tet1 in ES cell maintenance and inner cell mass cell specification. 0 D6 a9 k* ]1 q. b: SPMID: 20639862作者: lixiaodong 时间: 2010-8-12 12:40
ZhangY-NatRev6 m, g6 J D% J; F
Nat Rev Mol Cell Biol. 2010 Aug 4. [Epub ahead of print] $ ^& H7 @1 F9 h) }Active DNA demethylation: many roads lead to Rome. - N( p) f) ]0 a% U' }0 T9 XWu SC, Zhang Y. 0 j: A- x! @2 u) H. T$ R* O" i5 YHoward Hughes Medical Institute, and Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7295, USA.! w$ Y. A) Q. N' F+ I( q" O
Abstract 6 X, e) k- U! ~1 e; P( X2 ^$ @DNA methylation is one of the best-characterized epigenetic modifications and has been implicated in numerous biological processes, including transposable element silencing, genomic imprinting and X chromosome inactivation. Compared with other epigenetic modifications, DNA methylation is thought to be relatively stable. Despite its role in long-term silencing, DNA methylation is more dynamic than originally thought as active DNA demethylation has been observed during specific stages of development. In the past decade, many enzymes have been proposed to carry out active DNA demethylation and growing evidence suggests that, depending on the context, this process may be achieved by multiple mechanisms. Insight into how DNA methylation is dynamically regulated will broaden our understanding of epigenetic regulation and have great implications in somatic cell reprogramming and regenerative medicine. $ u3 `0 i8 J, [+ R4 Y+ GPMID: 20683471作者: ppcl2 时间: 2010-8-18 03:57