PUBLICATION
Uracil-DNA Glycosylase is involved in DNA demethylation and required for embryonic development in the zebrafish embryo
- Authors
- Wu, D., Chen, L., Sun, Q., Wu, X., Jia, S., Meng, A.
- ID
- ZDB-PUB-140513-134
- Date
- 2014
- Source
- The Journal of biological chemistry 289(22): 15463-15473 (Journal)
- Registered Authors
- Jia, Shunji, Meng, Anming, Wu, Di
- Keywords
- DNA demethylation, DNA glycosylase, DNA transcription, base excision repair (BER), embryo, nuclear reprogramming, zebrafish, zygotic genome activation
- MeSH Terms
-
- Animals
- Blastomeres/physiology
- Cellular Reprogramming/physiology
- Chromatin/metabolism
- DNA Methylation/physiology*
- DNA Repair/physiology
- Embryo, Nonmammalian/physiology*
- Gene Expression Regulation, Developmental*
- Gene Knockdown Techniques
- Transcription, Genetic/physiology
- Transcriptome
- Uracil/metabolism
- Uracil-DNA Glycosidase/genetics*
- Uracil-DNA Glycosidase/metabolism
- Zebrafish/embryology
- Zebrafish/genetics*
- PubMed
- 24739389 Full text @ J. Biol. Chem.
Citation
Wu, D., Chen, L., Sun, Q., Wu, X., Jia, S., Meng, A. (2014) Uracil-DNA Glycosylase is involved in DNA demethylation and required for embryonic development in the zebrafish embryo. The Journal of biological chemistry. 289(22):15463-15473.
Abstract
Uracil DNA glycosylase (Ung) is a component of base excision repair process and has the ability to remove uracil from U:G mispairs in DNA. However, its implications in development of vertebrate embryos are poorly understood. In this study, we found that zebrafish uracil-DNA glycosylase a (Unga) is maternally expressed at high levels and accumulated in nuclei during cleavage and blastulation periods. Knockdown of unga in zebrafish embryos causes an increase of the global DNA methylation level concomitantly with a reduction of overall transcriptional activity in the nucleus, ultimately resulting in embryonic lethality during segmentation period. Conversely, unga overexpression is sufficient to reduce the global DNA methylation level, to increase H3K4me3 and H3K27me3 marks and to activate genome transcription. Furthermore, overexpression of unga(D132A) mRNA, encoding a mutant Unga without DNA glycosylase activity, does not affect global DNA methylation level, indicating that its involvement in DNA demethylation is dependent on its glycosylase activity. These results together suggest that Unga is implicated in postfertilization genomic DNA demethylation, zygotic gene transcription and normal embryonic development in zebrafish.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping