title: UHRF2 regulates local 5-methylcytosine and suppresses spontaneous seizures.
abstract: The 5-methylcytosine (5mC) modification regulates multiple cellular processes and is faithfully maintained following DNA replication. In addition to DNA methyltransferase (DNMT) family proteins, ubiquitin-like PHD and ring finger domain-containing protein 1 (UHRF1) plays an important role in the maintenance of 5mC levels. Loss of UHRF1 abolishes 5mC in cells and leads to embryonic lethality in mice. Interestingly, UHRF1 has a paralog, UHRF2, that has similar sequence and domain architecture, but its biologic function is not clear. Here, we have generated Uhrf2 knockout mice and characterized the role of UHRF2 in vivo. Uhrf2 knockout mice are viable, but the adult mice develop frequent spontaneous seizures and display abnormal electrical activities in brain. Despite no global DNA methylation changes, 5mC levels are decreased at certain genomic loci in the brains of Uhrf2 knockout mice. Therefore, our study has revealed a unique role of UHRF2 in the maintenance of local 5mC levels in brain that is distinct from that of its paralog UHRF1.
authors.affiliation: a Key Laboratory of Reproductive Genetics, Ministry of Education and Women's Reproductive Health Laboratory of Zhejiang Province , Women's Hospital, School of Medicine, Zhejiang University , Hangzhou , Zhejiang , China.|b Institute of Translational Medicine, Zhejiang University , Hangzhou , Zhejiang , China.
authors.forename: Yidan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: a Key Laboratory of Reproductive Genetics, Ministry of Education and Women's Reproductive Health Laboratory of Zhejiang Province , Women's Hospital, School of Medicine, Zhejiang University , Hangzhou , Zhejiang , China.|b Institute of Translational Medicine, Zhejiang University , Hangzhou , Zhejiang , China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: a Key Laboratory of Reproductive Genetics, Ministry of Education and Women's Reproductive Health Laboratory of Zhejiang Province , Women's Hospital, School of Medicine, Zhejiang University , Hangzhou , Zhejiang , China.|b Institute of Translational Medicine, Zhejiang University , Hangzhou , Zhejiang , China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Meng
authors.affiliation: c Department of Molecular, Cellular, and Developmental Biology , University of Michigan , Ann Arbor , MI , USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Korn
authors.affiliation: c Department of Molecular, Cellular, and Developmental Biology , University of Michigan , Ann Arbor , MI , USA.
authors.forename: Jack M
authors.initials: JM
authors.lastname: Parent
authors.affiliation: a Key Laboratory of Reproductive Genetics, Ministry of Education and Women's Reproductive Health Laboratory of Zhejiang Province , Women's Hospital, School of Medicine, Zhejiang University , Hangzhou , Zhejiang , China.|b Institute of Translational Medicine, Zhejiang University , Hangzhou , Zhejiang , China.
authors.forename: Lin-Yu
authors.initials: LY
authors.lastname: Lu
authors.affiliation: d Department of Cancer Genetics and Epigenetics , Beckman Research Institute, City of Hope , Duarte , CA , USA.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Yu
mesh_terms: D044503:5-Methylcytosine / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000503:physiopathology; D058256:Brain Waves; D019175:DNA Methylation; D005260:Female; D008297:Male; D051379:Mice; D012640:Seizures / Q000235:genetics* / Q000503:physiopathology; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism
chemical_list: D044503:5-Methylcytosine; C571025:UHRF2 protein, mouse; D044767:Ubiquitin-Protein Ligases
keywords: 5-methylcytosine; Brain; seizure