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

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)66-74
Number of pages9
JournalFrontiers in Biology
Issue number1
StatePublished - Feb 2014


  • TET
  • active DNA demethylation
  • dentate granule neuron
  • methylome

ASJC Scopus subject areas

  • Biotechnology
  • Ecology, Evolution, Behavior and Systematics
  • Ecology
  • Genetics


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