DNA methylation;
G9a;
GLP;
histone lysine methylation;
D O I:
10.1038/emboj.2008.192
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
Methylation of DNA and lysine 9 of histone H3 (H3K9) are well-conserved epigenetic marks for transcriptional silencing. Although H3K9 methylation directs DNA methylation in filamentous fungi and plants, this pathway has not been corroborated in mammals. G9a and GLP/Eu-HMTase1 are two-related mammalian lysine methyltransferases and a G9a/GLP heteromeric complex regulates H3K9 methylation of euchromatin. To elucidate the function of G9a/GLP-mediated H3K9 methylation in the regulation of DNA methylation and transcriptional silencing, we characterized ES cells expressing catalytically inactive mutants of G9a and/or GLP. Interestingly, in ES cells expressing a G9a-mutant/GLP complex that does not rescue global H3K9 methylation, G9a/GLP-target genes remain silent. The CpG sites of the promoter regions of these genes were hypermethylated in such mutant ES cells, but hypomethylated in G9a-or GLP-KO ES cells. Treatment with a DNA methyltransferase inhibitor reactivates these G9a/GLP-target genes in ES cells expressing catalytically inactive G9a/GLP proteins, but not the wild-type proteins. This is the first clear evidence that G9a/GLP suppresses transcription by independently inducing both H3K9 and DNA methylation.
机构:
Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Cardiovasc Res Ctr, Charlestown, MA 02129 USAHarvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Cardiovasc Res Ctr, Charlestown, MA 02129 USA
Chen, TP
;
Ueda, Y
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Cardiovasc Res Ctr, Charlestown, MA 02129 USAHarvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Cardiovasc Res Ctr, Charlestown, MA 02129 USA
Ueda, Y
;
Xie, SP
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Cardiovasc Res Ctr, Charlestown, MA 02129 USAHarvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Cardiovasc Res Ctr, Charlestown, MA 02129 USA
Xie, SP
;
Li, E
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Cardiovasc Res Ctr, Charlestown, MA 02129 USAHarvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Cardiovasc Res Ctr, Charlestown, MA 02129 USA
机构:Univ Tokyo, Dept Anim Resource Sci & Vet Med Sci, Lab Cellular Biochem, Tokyo 1138657, Japan
Ikegami, Kohta
;
Iwatani, Misa
论文数: 0引用数: 0
h-index: 0
机构:Univ Tokyo, Dept Anim Resource Sci & Vet Med Sci, Lab Cellular Biochem, Tokyo 1138657, Japan
Iwatani, Misa
;
Suzuki, Masako
论文数: 0引用数: 0
h-index: 0
机构:Univ Tokyo, Dept Anim Resource Sci & Vet Med Sci, Lab Cellular Biochem, Tokyo 1138657, Japan
Suzuki, Masako
;
论文数: 引用数:
h-index:
机构:
Tachibana, Makoto
;
Shinkai, Yoichi
论文数: 0引用数: 0
h-index: 0
机构:Univ Tokyo, Dept Anim Resource Sci & Vet Med Sci, Lab Cellular Biochem, Tokyo 1138657, Japan
Shinkai, Yoichi
;
Tanaka, Satoshi
论文数: 0引用数: 0
h-index: 0
机构:Univ Tokyo, Dept Anim Resource Sci & Vet Med Sci, Lab Cellular Biochem, Tokyo 1138657, Japan
Tanaka, Satoshi
;
Greally, John M.
论文数: 0引用数: 0
h-index: 0
机构:Univ Tokyo, Dept Anim Resource Sci & Vet Med Sci, Lab Cellular Biochem, Tokyo 1138657, Japan
Greally, John M.
;
Yagi, Shintaro
论文数: 0引用数: 0
h-index: 0
机构:Univ Tokyo, Dept Anim Resource Sci & Vet Med Sci, Lab Cellular Biochem, Tokyo 1138657, Japan
Yagi, Shintaro
;
Hattori, Naka
论文数: 0引用数: 0
h-index: 0
机构:Univ Tokyo, Dept Anim Resource Sci & Vet Med Sci, Lab Cellular Biochem, Tokyo 1138657, Japan
Hattori, Naka
;
Shiota, Kunio
论文数: 0引用数: 0
h-index: 0
机构:
Univ Tokyo, Dept Anim Resource Sci & Vet Med Sci, Lab Cellular Biochem, Tokyo 1138657, JapanUniv Tokyo, Dept Anim Resource Sci & Vet Med Sci, Lab Cellular Biochem, Tokyo 1138657, Japan
机构:
Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Cardiovasc Res Ctr, Charlestown, MA 02129 USAHarvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Cardiovasc Res Ctr, Charlestown, MA 02129 USA
Chen, TP
;
Ueda, Y
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Cardiovasc Res Ctr, Charlestown, MA 02129 USAHarvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Cardiovasc Res Ctr, Charlestown, MA 02129 USA
Ueda, Y
;
Xie, SP
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Cardiovasc Res Ctr, Charlestown, MA 02129 USAHarvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Cardiovasc Res Ctr, Charlestown, MA 02129 USA
Xie, SP
;
Li, E
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Cardiovasc Res Ctr, Charlestown, MA 02129 USAHarvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Cardiovasc Res Ctr, Charlestown, MA 02129 USA
机构:Univ Tokyo, Dept Anim Resource Sci & Vet Med Sci, Lab Cellular Biochem, Tokyo 1138657, Japan
Ikegami, Kohta
;
Iwatani, Misa
论文数: 0引用数: 0
h-index: 0
机构:Univ Tokyo, Dept Anim Resource Sci & Vet Med Sci, Lab Cellular Biochem, Tokyo 1138657, Japan
Iwatani, Misa
;
Suzuki, Masako
论文数: 0引用数: 0
h-index: 0
机构:Univ Tokyo, Dept Anim Resource Sci & Vet Med Sci, Lab Cellular Biochem, Tokyo 1138657, Japan
Suzuki, Masako
;
论文数: 引用数:
h-index:
机构:
Tachibana, Makoto
;
Shinkai, Yoichi
论文数: 0引用数: 0
h-index: 0
机构:Univ Tokyo, Dept Anim Resource Sci & Vet Med Sci, Lab Cellular Biochem, Tokyo 1138657, Japan
Shinkai, Yoichi
;
Tanaka, Satoshi
论文数: 0引用数: 0
h-index: 0
机构:Univ Tokyo, Dept Anim Resource Sci & Vet Med Sci, Lab Cellular Biochem, Tokyo 1138657, Japan
Tanaka, Satoshi
;
Greally, John M.
论文数: 0引用数: 0
h-index: 0
机构:Univ Tokyo, Dept Anim Resource Sci & Vet Med Sci, Lab Cellular Biochem, Tokyo 1138657, Japan
Greally, John M.
;
Yagi, Shintaro
论文数: 0引用数: 0
h-index: 0
机构:Univ Tokyo, Dept Anim Resource Sci & Vet Med Sci, Lab Cellular Biochem, Tokyo 1138657, Japan
Yagi, Shintaro
;
Hattori, Naka
论文数: 0引用数: 0
h-index: 0
机构:Univ Tokyo, Dept Anim Resource Sci & Vet Med Sci, Lab Cellular Biochem, Tokyo 1138657, Japan
Hattori, Naka
;
Shiota, Kunio
论文数: 0引用数: 0
h-index: 0
机构:
Univ Tokyo, Dept Anim Resource Sci & Vet Med Sci, Lab Cellular Biochem, Tokyo 1138657, JapanUniv Tokyo, Dept Anim Resource Sci & Vet Med Sci, Lab Cellular Biochem, Tokyo 1138657, Japan