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J Biol Chem. 2017 Mar 17;292(11):4533-4543. doi: 10.1074/jbc.M116.754580. Epub 2017 Jan 23.

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

Author information

1
From the Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
2
the Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030.
3
the Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China.
4
the Key Laboratory of Brain Functional Genomics, Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, East China Normal University, Shanghai 200062, China.
5
the Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon 1, CNRS UMR5242, Ecole Normale Supérieure de Lyon, Lyon 69007, France, and.
6
From the Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China, jwli@bio.ecnu.edu.cn.
7
From the Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China, jmweng@bio.ecnu.edu.cn.
8
the Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, China.

Abstract

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.

KEYWORDS:

DNA demethylation; DNA methylation; dioxygenase; epigenetics; mouse genetics; neurobiology; protein-DNA interaction

PMID:
28115522
PMCID:
PMC5377770
DOI:
10.1074/jbc.M116.754580
[Indexed for MEDLINE]
Free PMC Article

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