The role and mechanism of DNA oxidation in epigenetic regulation of mammalian  development

Abstract:

DNA demethylation is thought to play a pivotal role in transcriptional activation of gene activity. However, both the molecular mechanism and biological relevance of DNA demethylation have remained enigmatic. Dr. Xu lab discovered that the Ten-eleven-translocation (Tet) dioxygenases oxidize the methylcytosine in DNA into 5-carboxylcytosine in mammals and this oxidized base is in turn recognized and excised by a DNA glycosylase, thus defining a pathway of oxidative demethylation. Further analysis indicates that Tet-mediated base oxidation directly contributes todemethylation of the sperm genome in fertilized eggs, enabling appropriate reactivation of pluripotency genes. These findings provide insights into the regulation of embryonic development and reveal a novel disease mechanism.
 
Dr. Xu is currently a Principal Investigator in the Institute of Biochemistry and Cell Biology, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences (CAS). He received his B.S.degree from Zhejiang University in 1985 and his doctorate in Genetics from the Max-Planck Institute for Molecular Genetics in Germany in 1993. His postdoctoral work was conducted in the Department of Genetics and Development of Columbia University, New York. After he returned to China in 2001, he received a prestigious award from the Max-Planck Society for independent young investigators.

Dr. Xu is interested in the epigenetic regulation of mammalian development. His lab recently discovered that the Ten-eleven-translocation (Tet) dioxygenases oxidize the methylcytosine in DNA into 5-carboxylcytosine in mammals and this oxidized base is in turn recognized and excised by a DNA glycosylase, thus defining a pathway of oxidative demethylation. Further analysis indicates that Tet-mediated base oxidation directly contributes to demethylation of the sperm genome in fertilized eggs, enabling appropriate reactivation of pluripotency genes. These findings provide insights into the regulation of embryonic development and reveal a novel disease mechanism.