第四期水木清华生命科学讲座系列

DNA Oxidation towards Totipotency in Mammalian Development

Guoliang Xu(徐国良), PhD

Principal Investigator

Institute of Biochemistry and Cell Biology

Chinese Academy of Sciences

Scientific awards/honors

One-Hundred-Talents Award of the Chinese Academy of Sciences (2001)

Distinguished Young Investigator Award from China NSF (2002)

Research interests

DNA methylation and oxidation, stem cells and epigenetic reprogramming

Academic activities

Reviewing Editor of J. Biol. Chem., Editorial advisor for Biochemical J. and academic editor for PLoS ONE; Referee for Science, Cell, Nature Communications, and Genes & Development etc.

Abstract

Mammalian development begins with a single cell resulted from the fertilization of a sperm and an oocyte. The early embryonic genome undergoes profound epigenetic reprogramming to prepare for development. The biological significance and mechanisms of epigenetic reprogramming are poorly understood. We find that 5-methylcytosine (5mC), the most abundant type of base modification, is oxidized to 5-hydroxymethylcytosine (5hmC) as well as 5-carboxymethylcytosine (5caC) specifically in the paternal genomic DNA in zygotes. In vitro, the Tet family of dioxygenases oxidize 5mC to 5caC under physiologically relevant conditions. In zygotes, Tet3 is responsible for the genome-wide conversion of 5mC to 5hmC and 5caC. Deficiency of zygotic Tet3 impedes demethylation at the paternal Oct4 and Nanog genes and delays the reactivation of Oct4 in early embryos. The heterozygous mutant embryos lacking maternal Tet3 suffer increased developmental failures. Importantly, oocytes lacking Tet3 also show impaired reprogramming of injected somatic cell nuclei. We conclude that Tet-mediated 5mC oxidation is important for DNA demethylation and gene activation in the early embryo following natural fertilization, as well as for the reprogramming of somatic cell nuclei during animal cloning.

Date: 4:00-5:00pm, Mar. 14(Thursday)

Venue: 143, New Biology Building