Genome-wide antagonism between 5-hydroxymethylcytosine and DNA methylation in the adult mouse brain  

作　　者：Junjie U. GUO Keith E. SZULWACH Yijing SU Yujing LI Bing YAO Zihui XU Joo Heon SH1N Bing XIE Yuan GAO Guo-li MING Peng JIN Hongjun SONG 

机构地区：[1]Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA [2]The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA [3]Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. [4]Department of Human Genetics, Emory University School of Medicine, 615 Michael Street, Atlanta, GA 30322, USA [5]Lieber Institute for Brain Development, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA

出　　处：《Frontiers in Biology》2014年第1期66-74,共9页生物学前沿（英文版）

摘　　要：Mounting evidence points to critical roles for DNA modifications, including 5-methylcytosine （5mC） and its oxidized forms, in the development, plasticity and disorders of the mammalian nervous system. The novel DNA base 5- hydroxymethylcytosine （5hmC） is known to be capable of initiating passive or active DNA demethylation, but whether and how extensively 5hmC functions in shaping the post-mitotic neuronal DNA methylome is unclear. Here we report the genome-wide distribution of 5hmC in dentate granule neurons from adult mouse hippocampus in vivo. 5hmC in the neuronal genome is highly enriched in gene bodies, especially in exons, and correlates with gene expression. Direct genome-wide comparison of 5hmC distribution between embryonic stem cells and neurons reveals extensive differences, reflecting the functional disparity between these two cell types. Importantly, integrative analysis of 5hmC, overall DNA methylation and gene expression profiles of dentate granule neurons in vivo reveals the genome-wide antagonism between these two states of cytosine modifications, supporting a role for 5hmC in shaping the neuronal DNA methylome by promoting active DNA demethylation.Mounting evidence points to critical roles for DNA modifications, including 5-methylcytosine （5mC） and its oxidized forms, in the development, plasticity and disorders of the mammalian nervous system. The novel DNA base 5- hydroxymethylcytosine （5hmC） is known to be capable of initiating passive or active DNA demethylation, but whether and how extensively 5hmC functions in shaping the post-mitotic neuronal DNA methylome is unclear. Here we report the genome-wide distribution of 5hmC in dentate granule neurons from adult mouse hippocampus in vivo. 5hmC in the neuronal genome is highly enriched in gene bodies, especially in exons, and correlates with gene expression. Direct genome-wide comparison of 5hmC distribution between embryonic stem cells and neurons reveals extensive differences, reflecting the functional disparity between these two cell types. Importantly, integrative analysis of 5hmC, overall DNA methylation and gene expression profiles of dentate granule neurons in vivo reveals the genome-wide antagonism between these two states of cytosine modifications, supporting a role for 5hmC in shaping the neuronal DNA methylome by promoting active DNA demethylation.

关 键 词：dentate granule neuron active DNA demethylation TET methylome 

分 类 号：Q75[生物学—分子生物学] Q78