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

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.

journal_name

Cell Rep

journal_title

Cell reports

authors

Cheng Y,Sun M,Chen L,Li Y,Lin L,Yao B,Li Z,Wang Z,Chen J,Miao Z,Xin N,Huang L,Allen EG,Wu H,Xu X,Jin P

doi

10.1016/j.celrep.2018.11.061

subject

Has Abstract

pub_date

2018-12-11 00:00:00

pages

3194-3203.e4

issue

11

issn

2211-1247

pii

S2211-1247(18)31837-0

journal_volume

25

pub_type

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