Volume 21, No 12, Dec 2011
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 21 Issue 12, December 2011: 1670-1676
ORIGINAL ARTICLES
Generation and replication-dependent dilution of 5fC and 5caC during mouse preimplantation development
>Azusa Inoue1,2, Li Shen1,2, Qing Dai3, Chuan He3 and Yi Zhang1,2
1Howard Hughes Medical Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
2Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
3Department of Chemistry and Institute for Biophysical Dynamics, the University of Chicago, Chicago, IL 60637, USA
Correspondence: Yi Zhang,(yi_zhang@med.unc.edu)
One of the recent advances in the epigenetic field is the demonstration that the Tet family of proteins are capable of catalyzing conversion of 5-methylcytosine (5mC) of DNA to 5-hydroxymethylcytosine (5hmC). Interestingly, recent studies have shown that 5hmC can be further oxidized by Tet proteins to generate 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC), which can be removed by thymine DNA glycosylase (TDG). To determine whether Tet-catalyzed conversion of 5mC to 5fC and 5caC occurs in vivo in zygotes, we generated antibodies specific for 5fC and 5caC. By immunostaining, we demonstrate that loss of 5mC in the paternal pronucleus is concurrent with the appearance of 5fC and 5caC, similar to that of 5hmC. Importantly, instead of being quickly removed through an enzyme-catalyzed process, both 5fC and 5caC exhibit replication-dependent dilution during mouse preimplantation development. These results not only demonstrate the conversion of 5mC to 5fC and 5caC in zygotes, but also indicate that both 5fC and 5caC are relatively stable and may be functional during preimplantation development. Together with previous studies, our study suggests that Tet-catalyzed conversion of 5mC to 5hmC/5fC/5caC followed by replication-dependent dilution accounts for paternal DNA demethylation during preimplantation development.
Cell Research (2011) 21:1670-1676. doi:10.1038/cr.2011.189; published online 29 November 2011
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