UHRF2 has been implicated as a novel regulator for both DNA methylation (5mC) and hydroxymethylation (5hmC), but its physiological function and role in DNA methylation/ hydroxymethylation are unknown. Here we show that in mice, UHRF2 is more abundantly expressed in the brain and a few other tissues. Uhrf2 knock-out mice are viable and fertile and exhibit no gross defect. Although there is no significant change of DNA methylation, the Uhrf2 null mice exhibit a reduction of 5hmC in the brain, including the cortex and hippocampus. Furthermore, the Uhrf2 null mice exhibit a partial impairment in spatial memory acquisition and retention. Consistent with the phenotype, gene expression profiling uncovers a role for UHRF2 in regulating neuron-related gene expression. Finally, we provide evidence that UHRF2 binds 5hmC in cells but does not appear to affect the TET1 enzymatic activity. Together, our study supports UHRF2 as a bona fide 5hmC reader and further demonstrates a role for 5hmC in neuronal function.
[1]East China Normal Univ, Inst Biomed Sci & Sch Life Sci, Shanghai Key Lab Regulatory Biol, 500 Dongchuan Rd, Shanghai 200241, Peoples R China;
[2]Baylor Coll Med, Dept Mol Physiol & Biophys, Houston, TX 77030 USA;
[3]Chinese Acad Sci, Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China;
[4]China Normal Univ, Shanghai Key Lab Brain Funct Genom, Key Lab Brain Funct Genom, Minist Educ, Shanghai 200062, Peoples R China;
[5]Univ Lyon 1, CNRS, UMR5242, Inst Genom Fonctionnelle Lyon, F-69007 Lyon, France;
[6]Sun Yat Sen Univ, Ctr Canc, Collaborat Innovat Ctr Canc Med, Guangzhou 510060, Peoples R China
(8.0+极速模式)