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

Junjie U Guo; Keith E Szulwach; Yijing Su; Yujing Li; Bing Yao; Zihui Xu; Joo Heon Shin; Bing Xie; Yuan Gao; Guo-Li Ming; Peng Jin; Hongjun Song

doi:10.1007/s11515-014-1295-1

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

Front Biol (Beijing). 2014 Feb;9(1):66-74. doi: 10.1007/s11515-014-1295-1.

Authors

Junjie U Guo¹, Keith E Szulwach², Yijing Su³, Yujing Li², Bing Yao², Zihui Xu², Joo Heon Shin⁴, Bing Xie⁴, Yuan Gao⁵, Guo-Li Ming¹, Peng Jin², Hongjun Song¹

Affiliations

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

Abstract

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.

Keywords: TET; active DNA demethylation; dentate granule neuron; methylome.

Abstract

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