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.
基金:
National Science and Technology Major Project "Key New Drug Creation and Manufacturing Program" of China [2014ZX09507002-002]; Ministry of Science and Technology of ChinaMinistry of Science and Technology, China [2015CB910402, 2015CB856200]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [91419303, 91219202, 31525013]; Science and Technology Commission of Shanghai MunicipalityScience & Technology Commission of Shanghai Municipality (STCSM) [14XD1401700, 11DZ2260300]
语种:
外文
被引次数:
WOS:
PubmedID:
中科院(CAS)分区:
出版当年[2017]版:
大类|2 区生物
小类|2 区生化与分子生物学
最新[2023]版:
大类|2 区生物学
小类|2 区生化与分子生物学
第一作者:
第一作者机构:[1]East China Normal Univ, Inst Biomed Sci & Sch Life Sci, Shanghai Key Lab Regulatory Biol, 500 Dongchuan Rd, Shanghai 200241, Peoples R China;
通讯作者:
通讯机构:[1]East China Normal Univ, Inst Biomed Sci & Sch Life Sci, Shanghai Key Lab Regulatory Biol, 500 Dongchuan Rd, Shanghai 200241, Peoples R China;[6]Sun Yat Sen Univ, Ctr Canc, Collaborat Innovat Ctr Canc Med, Guangzhou 510060, Peoples R China
推荐引用方式(GB/T 7714):
Chen Ruoyu,Zhang Qiao,Duan Xiaoya,et al.The 5-Hydroxymethylcytosine (5hmC) Reader UHRF2 Is Required for Normal Levels of 5hmC in Mouse Adult Brain and Spatial Learning and Memory[J].JOURNAL OF BIOLOGICAL CHEMISTRY.2017,292(11):4533-4543.doi:10.1074/jbc.M116.754580.
APA:
Chen, Ruoyu,Zhang, Qiao,Duan, Xiaoya,York, Philippe,Chen, Guo-Dong...&Wong, Jiemin.(2017).The 5-Hydroxymethylcytosine (5hmC) Reader UHRF2 Is Required for Normal Levels of 5hmC in Mouse Adult Brain and Spatial Learning and Memory.JOURNAL OF BIOLOGICAL CHEMISTRY,292,(11)
MLA:
Chen, Ruoyu,et al."The 5-Hydroxymethylcytosine (5hmC) Reader UHRF2 Is Required for Normal Levels of 5hmC in Mouse Adult Brain and Spatial Learning and Memory".JOURNAL OF BIOLOGICAL CHEMISTRY 292..11(2017):4533-4543