title: The 5-Hydroxymethylcytosine (5hmC) Reader UHRF2 Is Required for Normal Levels of 5hmC in Mouse Adult Brain and Spatial Learning and Memory.
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.Uhrf2knock-out mice are viable and fertile and exhibit no gross defect. Although there is no significant change of DNA methylation, theUhrf2null mice exhibit a reduction of 5hmC in the brain, including the cortex and hippocampus. Furthermore, theUhrf2null 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 abona fide5hmC reader and further demonstrates a role for 5hmC in neuronal function.
authors.affiliation: From the Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
authors.forename: Ruoyu
authors.initials: R
authors.lastname: Chen
authors.affiliation: From the Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: From the Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
authors.forename: Xiaoya
authors.initials: X
authors.lastname: Duan
authors.affiliation: the Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030.
authors.forename: Philippe
authors.initials: P
authors.lastname: York
authors.affiliation: the Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Guo-Dong
authors.initials: GD
authors.lastname: Chen
authors.affiliation: the Key Laboratory of Brain Functional Genomics, Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, East China Normal University, Shanghai 200062, China.
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Yin
authors.affiliation: From the Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
authors.forename: Haijun
authors.initials: H
authors.lastname: Zhu
authors.affiliation: the Key Laboratory of Brain Functional Genomics, Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, East China Normal University, Shanghai 200062, China.
authors.forename: Meichen
authors.initials: M
authors.lastname: Xu
authors.affiliation: From the Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
authors.forename: Peilin
authors.initials: P
authors.lastname: Chen
authors.affiliation: From the Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
authors.forename: Qihan
authors.initials: Q
authors.lastname: Wu
authors.affiliation: From the Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
authors.forename: Dali
authors.initials: D
authors.lastname: Li
authors.affiliation: the Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon 1, CNRS UMR5242, Ecole Normale Supérieure de Lyon, Lyon 69007, France, and.
authors.forename: Jacques
authors.initials: J
authors.lastname: Samarut
authors.affiliation: the Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Guoliang
authors.initials: G
authors.lastname: Xu
authors.affiliation: the Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030.
authors.forename: Pumin
authors.initials: P
authors.lastname: Zhang
authors.affiliation: the Key Laboratory of Brain Functional Genomics, Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, East China Normal University, Shanghai 200062, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Cao
authors.affiliation: 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.
authors.forename: Jiwen
authors.initials: J
authors.lastname: Li
authors.affiliation: 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.|the Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, China.
authors.forename: Jiemin
authors.initials: J
authors.lastname: Wong
mesh_terms: D044503:5-Methylcytosine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000502:physiology*; D001923:Brain Chemistry; D002460:Cell Line; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008124:Locomotion; D008297:Male; D008568:Memory; D051379:Mice; D018345:Mice, Knockout; D065853:Spatial Learning; D044767:Ubiquitin-Protein Ligases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*
chemical_list: C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; C571025:UHRF2 protein, mouse; D044767:Ubiquitin-Protein Ligases
keywords: DNA demethylation; DNA methylation; dioxygenase; epigenetics; mouse genetics; neurobiology; protein-DNA interaction