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Effects of intracerebral hemorrhage on 5-hydroxymethylcytosine modification in mouse brains

Authors Tang Y, Han S, Asakawa T, Luo Y, Han X, Xiao B, Dong Q, Wang L

Received 30 September 2015

Accepted for publication 7 January 2016

Published 15 March 2016 Volume 2016:12 Pages 617—624

DOI https://doi.org/10.2147/NDT.S97456

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Chin-Pang Lee

Peer reviewer comments 3

Editor who approved publication: Professor Wai Kwong Tang


Yilin Tang,1,* Sha Han,1,* Tetsuya Asakawa,2,3 Yunhe Luo,1 Xiang Han,1 Baoguo Xiao,4 Qiang Dong,1,4 Liang Wang1,4

1Department of Neurology, Huashan Hospital of Fudan University, Shanghai, People’s Republic of China; 2Department of Neurosurgery, 3Department of Psychiatry, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan; 4Institute of Neurology, Huashan Hospital of Fudan University, Shanghai, People’s Republic of China

*These authors contributed equally to this work

Abstract: The past decade has resulted in an increase in the knowledge of molecular mechanisms underlying brain injury induced by intracerebral hemorrhage (ICH). Recent advances have provided a link between epigenetic modification and the regulation of gene expression. 5-hydroxymethylcytosine (5hmC) converted from 5-methylcytosine by the ten-eleven translocation (TET) family of proteins has emerged as a new epigenetic modification. While the dynamics of 5hmC during cerebral ischemia have recently been reported, whether 5hmC is involved in ICH remains unexplored. In this study, we investigated the effects of ICH on DNA hydroxymethylation. We showed that the global level of 5hmC rapidly decreased as early as 24 hours after ICH and persisted until 72 hours. Furthermore, the level of 5hmC in the CpG-rich regions of Akt2, Pdpk1 and Vegf genes was significantly decreased with a minimum level observed at 48 hours or 72 hours. Decreased 5hmC was observed in parallel with an increase in 5-methylcytosine over this time course, and mRNA levels of Akt2, Pdpk1 and Vegf were downregulated upon ICH injury. Finally, Tet1, Tet2 and Tet3 mRNA levels were dramatically decreased in the ICH brain. Our study for the first time established the correlation between DNA hydroxymethylation and ICH injury. Further investigations should examine whether 5hmC modification could be a therapeutic target for the treatment of ICH injury.

Keywords: stroke, cerebral edema, DNA hydroxymethylation, TET protein

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