scholarly journals A DNA signal from the Thy-1 gene defines de novo methylation patterns in embryonic stem cells.

1990 ◽  
Vol 10 (8) ◽  
pp. 4396-4400 ◽  
Author(s):  
M Szyf ◽  
G Tanigawa ◽  
P L McCarthy

Although DNA can be extensively methylated de novo when introduced into pluripotent cells, the CpG island in the Thy-1 gene does not become methylated either in the mouse embryo or in embryonic stem cells. A 214-base-pair region near the promoter of the Thy-1 gene protects itself as well as heterologous DNA sequences from de novo methylation. We propose that this nucleotide sequence is representative of a class of important signals that limits de novo methylation in the embryo and establishes the pattern of hypomethylated CpG dinucleotides found in somatic tissues.

1990 ◽  
Vol 10 (8) ◽  
pp. 4396-4400
Author(s):  
M Szyf ◽  
G Tanigawa ◽  
P L McCarthy

Although DNA can be extensively methylated de novo when introduced into pluripotent cells, the CpG island in the Thy-1 gene does not become methylated either in the mouse embryo or in embryonic stem cells. A 214-base-pair region near the promoter of the Thy-1 gene protects itself as well as heterologous DNA sequences from de novo methylation. We propose that this nucleotide sequence is representative of a class of important signals that limits de novo methylation in the embryo and establishes the pattern of hypomethylated CpG dinucleotides found in somatic tissues.


2017 ◽  
Vol 50 (1) ◽  
pp. 83-95 ◽  
Author(s):  
Nipun Verma ◽  
Heng Pan ◽  
Louis C. Doré ◽  
Abhijit Shukla ◽  
Qing V. Li ◽  
...  

Gene ◽  
2002 ◽  
Vol 289 (1-2) ◽  
pp. 41-48 ◽  
Author(s):  
Jonathan E. Dodge ◽  
Bernard H. Ramsahoye ◽  
Z.Galen Wo ◽  
Masaki Okano ◽  
En Li

Development ◽  
1996 ◽  
Vol 122 (10) ◽  
pp. 3195-3205 ◽  
Author(s):  
H. Lei ◽  
S.P. Oh ◽  
M. Okano ◽  
R. Juttermann ◽  
K.A. Goss ◽  
...  

It has been a controversial issue as to how many DNA cytosine methyltransferase mammalian cells have and whether de novo methylation and maintenance methylation activities are encoded by a single gene or two different genes. To address these questions, we have generated a null mutation of the only known mammalian DNA methyltransferase gene through homologous recombination in mouse embryonic stem cells and found that the development of the homozygous embryos is arrested prior to the 8-somite stage. Surprisingly, the null mutant embryonic stem cells are viable and contain low but stable levels of methyl cytosine and methyltransferase activity, suggesting the existence of a second DNA methyltransferase in mammalian cells. Further studies indicate that de novo methylation activity is not impaired by the mutation as integrated provirus DNA in MoMuLV-infected homozygous embryonic stem cells become methylated at a similar rate as in wild-type cells. Differentiation of mutant cells results in further reduction of methyl cytosine levels, consistent with the de novo methylation activity being down regulated in differentiated cells. These results provide the first evidence that an independently encoded DNA methyltransferase is present in mammalian cells which is capable of de novo methylating cellular and viral DNA in vivo.


2017 ◽  
Vol 50 (5) ◽  
pp. 764-764
Author(s):  
Nipun Verma ◽  
Heng Pan ◽  
Louis C. Doré ◽  
Abhijit Shukla ◽  
Qing V. Li ◽  
...  

2017 ◽  
Vol 50 (5) ◽  
pp. 764-764
Author(s):  
Nipun Verma ◽  
Heng Pan ◽  
Louis C. Doré ◽  
Abhijit Shukla ◽  
Qing V. Li ◽  
...  

Stem Cells ◽  
2014 ◽  
Vol 32 (11) ◽  
pp. 2869-2879 ◽  
Author(s):  
Kate Hawkins ◽  
Maria Keramari ◽  
Francesca Soncin ◽  
Joe M. Segal ◽  
Lisa Mohamet ◽  
...  

2007 ◽  
Vol 27 (24) ◽  
pp. 8748-8759 ◽  
Author(s):  
Jing-Yu Li ◽  
Min-Tie Pu ◽  
Ryutaro Hirasawa ◽  
Bin-Zhong Li ◽  
Yan-Nv Huang ◽  
...  

ABSTRACT DNA methylation plays an important role in gene silencing in mammals. Two de novo methyltransferases, Dnmt3a and Dnmt3b, are required for the establishment of genomic methylation patterns in development. However, little is known about their coordinate function in the silencing of genes critical for embryonic development and how their activity is regulated. Here we show that Dnmt3a and Dnmt3b are the major components of a native complex purified from embryonic stem cells. The two enzymes directly interact and mutually stimulate each other both in vitro and in vivo. The stimulatory effect is independent of the catalytic activity of the enzyme. In differentiating embryonic carcinoma or embryonic stem cells and mouse postimplantation embryos, they function synergistically to methylate the promoters of the Oct4 and Nanog genes. Inadequate methylation caused by ablating Dnmt3a and Dnmt3b is associated with dysregulated expression of Oct4 and Nanog during the differentiation of pluripotent cells and mouse embryonic development. These results suggest that Dnmt3a and Dnmt3b form a complex through direct contact in living cells and cooperate in the methylation of the promoters of Oct4 and Nanog during cell differentiation. The physical and functional interaction between Dnmt3a and Dnmt3b represents a novel regulatory mechanism to ensure the proper establishment of genomic methylation patterns for gene silencing in development.


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