title: Uracil-DNA glycosylase is involved in DNA demethylation and required for embryonic development in the zebrafish embryo.
abstract: Uracil-DNA glycosylase (Ung) is a component of the 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.
authors.affiliation: From the State-Key Laboratory of Biomembrane and Membrane Engineering, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.affiliation: From the State-Key Laboratory of Biomembrane and Membrane Engineering, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Luxi
authors.initials: L
authors.lastname: Chen
authors.affiliation: From the State-Key Laboratory of Biomembrane and Membrane Engineering, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Qingrui
authors.initials: Q
authors.lastname: Sun
authors.affiliation: From the State-Key Laboratory of Biomembrane and Membrane Engineering, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Xiaotong
authors.initials: X
authors.lastname: Wu
authors.affiliation: From the State-Key Laboratory of Biomembrane and Membrane Engineering, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Shunji
authors.initials: S
authors.lastname: Jia
authors.affiliation: From the State-Key Laboratory of Biomembrane and Membrane Engineering, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China mengam@mail.tsinghua.edu.cn.
authors.forename: Anming
authors.initials: A
authors.lastname: Meng
mesh_terms: D000818:Animals; D001757:Blastomeres / Q000502:physiology; D065150:Cellular Reprogramming / Q000502:physiology; D002843:Chromatin / Q000378:metabolism; D019175:DNA Methylation / Q000502:physiology*; D004260:DNA Repair / Q000502:physiology; D004625:Embryo, Nonmammalian / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D014158:Transcription, Genetic / Q000502:physiology; D059467:Transcriptome; D014498:Uracil / Q000378:metabolism; D051981:Uracil-DNA Glycosidase / Q000235:genetics* / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology / Q000235:genetics*
chemical_list: D002843:Chromatin; D014498:Uracil; D051981:Uracil-DNA Glycosidase
keywords: Base Excision Repair (BER); DNA Demethylation; DNA Glycosylase; DNA Transcription; Embryo; Nuclear Reprogramming; Zebrafish; Zygotic Genome Activation
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