Epigenetic Regulation Mechanism of Key Signaling Pathways During Embryonic Development

5-Methylcytosine is a stable epigenetic modification of mammalian genomic DNA that is catalyzed by DNA methyltransferases (DNMTs). Recent studies have found that the TET family (TET1/2/3) of dioxygenases can oxidize 5-methylcytosine and lead to DNA demethylation. Although cytosine methylation has key roles in several processes such as genomic imprinting and X-chromosome inactivation, the functional significance of DNA methylation and demethylation in mouse embryogenesis has not been fully determined. 

Dr. XU Guoliang's group at the Institute of Biochemistry and Cell Biology (SIBCB), Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), in collaboration with Prof. Sun Xin at the University of Wisconsin and Prof. TANG Fuchou at Peking University, established the TET triple-knockout mouse model to inactivate all three TET genes in mice and analyzed the mechanism of embryo death caused by TET deletion.

They found that TET-mediated DNA oxidation modulates Lefty-Nodal signaling by promoting demethylation and/or antagonizing de novo methylation at the common target genes shared with DNMT3A and DNMT3B methyltransferases, and finally control gastrulation phenotypes. 

This study, for the first time, systematically revealed the epigenetic regulation mechanism of key signaling pathways during embryonic development, providing a new understanding of the basic principles of developmental biology. 

Related work was published in Nature on Oct. 19, 2016.

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