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The 5-Hydroxymethylcytosine (5hmC) Reader UHRF2 Is Required for Normal Levels of 5hmC in Mouse Adult Brain and Spatial Learning and Memory.

Chen, Ruoyu; Zhang, Qiao; Duan, Xiaoya; York, Philippe; Chen, Guo-Dong; Yin, Pengcheng; Zhu, Haijun; Xu, Meichen; Chen, Peilin; Wu, Qihan; Li, Dali; Samarut, Jacques; Xu, Guoliang; Zhang, Pumin; Cao, Xiaohua; Li, Jiwen; Wong, Jiemin.
J Biol Chem; 292(11): 4533-4543, 2017 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-28115522
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.
Selo DaSilva