UHRF2 regulates local 5-methylcytosine and suppresses spontaneous seizures [RNA-seq]

5-methylcytosine (5mC) regulates multiple cellular processes and is faithfully maintained following DNA replication. Ubiquitin-like PHD and ring finger domain-containing protein 1 (UHRF1) plays an important role in the maintenance of 5mC levels. Interestingly, UHRF1 has a paralog UHRF2 that has similar sequence and domain architecture, but the biological function of UHRF2 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. To explore possible mechanism beyond these phenomenon, we utilized high-throughput sequencing to identify global expression changes in Uhrf2 knockout mice brains. In addition, we explored genome-wide 5mc profiles in these samples to examine if UHRF2 regulates 5mc levels in specific genome loci. Overall design: Examination of global gene expressions in brains of wild type and Uhrf2 knockout mice by RNA-seq.

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Liu Y, Zhang B, Meng X, Korn MJ, Parent JM, Lu LY, Yu X