Transcriptional activation of transposable elements in mouse zygotes is independent of Tet3-mediated 5-methylcytosine oxidation
- 27 November 2012
- journal article
- Published by Springer Science and Business Media LLC in Cell Research
- Vol. 22 (12), 1640-1649
- https://doi.org/10.1038/cr.2012.160
Abstract
The methylation state of the paternal genome is rapidly reprogrammed shortly after fertilization. Recent studies have revealed that loss of 5-methylcytosine (5mC) in zygotes correlates with appearance of 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). This process is mediated by Tet3 and the 5mC oxidation products generated in zygotes are gradually lost during preimplantation development through a replication-dependent dilution process. Despite these findings, the biological significance of Tet3-mediated oxidation of 5mC to 5hmC/5fC/5caC in zygotes is unknown. DNA methylation plays an important role in silencing gene expression including the repression of transposable elements (TEs). Given that the activation of TEs during preimplantation development correlates with loss of DNA methylation, it is believed that paternal DNA demethylation may have an important role in TE activation. Here we examined this hypothesis and found that Tet3-mediated 5mC oxidation does not have a significant contribution to TE activation. We show that the expression of LINE-1 (long interspersed nucleotide element 1) and ERVL (endogenous retroviruses class III) are activated from both paternal and maternal genomes in zygotes. Inhibition of 5mC oxidation by siRNA-mediated depletion of Tet3 affected neither TE activation, nor global transcription in zygotes. Thus, our study provides the first evidence demonstrating that activation of both TEs and global transcription in zygotes are independent of Tet3-mediated 5mC oxidation.Keywords
This publication has 45 references indexed in Scilit:
- A unique regulatory phase of DNA methylation in the early mammalian embryoNature, 2012
- Mechanisms and functions of Tet protein-mediated 5-methylcytosine oxidationGenes & Development, 2011
- Generation and replication-dependent dilution of 5fC and 5caC during mouse preimplantation developmentCell Research, 2011
- Thymine DNA Glycosylase Can Rapidly Excise 5-Formylcytosine and 5-Carboxylcytosine: POTENTIAL IMPLICATIONS FOR ACTIVE DEMETHYLATION OF CpG SITESPublished by Elsevier BV ,2011
- Reprogramming of the paternal genome upon fertilization involves genome-wide oxidation of 5-methylcytosineProceedings of the National Academy of Sciences of the United States of America, 2011
- A Strand-Specific Burst in Transcription of Pericentric Satellites Is Required for Chromocenter Formation and Early Mouse DevelopmentDevelopmental Cell, 2010
- Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specificationNature, 2010
- Dynamic link of DNA demethylation, DNA strand breaks and repair in mouse zygotesThe EMBO Journal, 2010
- Small RNA class transition from siRNA/piRNA to miRNA during pre-implantation mouse developmentNucleic Acids Research, 2010
- Structural differences in centromeric heterochromatin are spatially reconciled on fertilisation in the mouse zygoteChromosoma, 2007