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Publication : UHRF2 regulates local 5-methylcytosine and suppresses spontaneous seizures.

First Author  Liu Y Year  2017
Journal  Epigenetics Volume  12
Issue  7 Pages  551-560
PubMed ID  28402695 Mgi Jnum  J:262684
Mgi Id  MGI:6161959 Doi  10.1080/15592294.2017.1314423
Citation  Liu Y, et al. (2017) UHRF2 regulates local 5-methylcytosine and suppresses spontaneous seizures. Epigenetics 12(7):551-560
abstractText  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.
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