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Cell Rep. 2018 Dec 11;25(11):3194-3203.e4. doi: 10.1016/j.celrep.2018.11.061.

Ten-Eleven Translocation Proteins Modulate the Response to Environmental Stress in Mice.

Author information

1
Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
2
The Institute of Neuroscience, Soochow University, Suzhou City 215006, P.R. China; Institute for Fetology, the First Affiliated Hospital of Soochow University, Suzhou City 215006, P.R. China.
3
Department of Biostatistics and Bioinformatics, Emory University Rollins School of Public Health, Atlanta, GA 30322, USA.
4
The Institute of Neuroscience, Soochow University, Suzhou City 215006, P.R. China.
5
The Institute of Neuroscience, Soochow University, Suzhou City 215006, P.R. China. Electronic address: xingshunxu@suda.edu.cn.
6
Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: peng.jin@emory.edu.

Abstract

5-hydroxymethylcytosine (5hmC) is enriched in brain and has been recognized as an important DNA modification. However, the roles of 5hmC and its writers, ten-eleven translocation (Tet) proteins, in stress-induced response have yet to be elucidated. Here, we show that chronic restraint stress (CRS) induced depression-like behavior in mice and resulted in a 5hmC reduction in prefrontal cortex (PFC). We found that loss of Tet1 (Tet1 KO) led to resistance to CRS, whereas loss of Tet2 (Tet2 KO) increased the susceptibility of mice to CRS. Genome-wide 5hmC profiling identified the phenotype-associated stress-induced dynamically hydroxymethylated loci (PA-SI-DhMLs), which are strongly enriched with hypoxia-induced factor (HIF) binding motifs. We demonstrated the physical interaction between TET1 and HIF1α induced by CRS and revealed that the increased HIF1α binding under CRS is associated with SI-DhMLs. These results suggest that TET1 could regulate stress-induced response by interacting with HIF1α.

KEYWORDS:

5-hydroxymethylcytosine; Tet protein; depression; prefrontal cortex; stress

PMID:
30540950
PMCID:
PMC6350936
DOI:
10.1016/j.celrep.2018.11.061
[Indexed for MEDLINE]
Free PMC Article

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