PMID- 27125313
OWN - NLM
STAT- MEDLINE
DCOM- 20180116
LR  - 20181113
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 6
DP  - 2016 Apr 29
TI  - High activity of the stress promoter contributes to susceptibility to stress in 
      the tree shrew.
PG  - 24905
LID - 10.1038/srep24905 [doi]
LID - 24905
AB  - Stress is increasingly present in everyday life in our fast-paced society and 
      involved in the pathogenesis of many psychiatric diseases. 
      Corticotrophin-releasing-hormone (CRH) plays a pivotal role in regulating the 
      stress responses. The tree shrews are highly vulnerable to stress which makes 
      them the promising animal models for studying stress responses. However, the 
      mechanisms underlying their high stress-susceptibility remained unknown. Here we 
      confirmed that cortisol was the dominate corticosteroid in tree shrew and was 
      significantly increased after acute stress. Our study showed that the function of 
      tree shrew CRH - hypothalamic-pituitary-adrenal (HPA) axis was nearly identical 
      to human that contributed little to their hyper-responsiveness to stress. Using 
      CRH transcriptional regulation analysis we discovered a peculiar active 
      glucocorticoid receptor response element (aGRE) site within the tree shrew CRH 
      promoter, which continued to recruit co-activators including SRC-1 (steroid 
      receptor co-activator-1) to promote CRH transcription under basal or 
      forskolin/dexamethasone treatment conditions. Basal CRH mRNA increased when the 
      aGRE was knocked into the CRH promoter in human HeLa cells using CAS9/CRISPR. The 
      aGRE functioned critically to form the "Stress promoter" that contributed to the 
      higher CRH expression and susceptibility to stress. These findings implicated 
      novel molecular bases of the stress-related diseases in specific populations.
FAU - Fang, Hui
AU  - Fang H
AD  - CAS Key Laboratory of Brain Function and Disease, School of Life Science, 
      University of Science and Technology of China, Huangshan Road 443, Hefei 230027, 
      Anhui, China.
FAU - Sun, Yun-Jun
AU  - Sun YJ
AD  - CAS Key Laboratory of Brain Function and Disease, School of Life Science, 
      University of Science and Technology of China, Huangshan Road 443, Hefei 230027, 
      Anhui, China.
FAU - Lv, Yan-Hong
AU  - Lv YH
AD  - CAS Key Laboratory of Brain Function and Disease, School of Life Science, 
      University of Science and Technology of China, Huangshan Road 443, Hefei 230027, 
      Anhui, China.
FAU - Ni, Rong-Jun
AU  - Ni RJ
AD  - CAS Key Laboratory of Brain Function and Disease, School of Life Science, 
      University of Science and Technology of China, Huangshan Road 443, Hefei 230027, 
      Anhui, China.
FAU - Shu, Yu-Mian
AU  - Shu YM
AD  - CAS Key Laboratory of Brain Function and Disease, School of Life Science, 
      University of Science and Technology of China, Huangshan Road 443, Hefei 230027, 
      Anhui, China.
FAU - Feng, Xiu-Yu
AU  - Feng XY
AD  - CAS Key Laboratory of Brain Function and Disease, School of Life Science, 
      University of Science and Technology of China, Huangshan Road 443, Hefei 230027, 
      Anhui, China.
FAU - Wang, Yu
AU  - Wang Y
AD  - CAS Key Laboratory of Brain Function and Disease, School of Life Science, 
      University of Science and Technology of China, Huangshan Road 443, Hefei 230027, 
      Anhui, China.
FAU - Shan, Qing-Hong
AU  - Shan QH
AD  - CAS Key Laboratory of Brain Function and Disease, School of Life Science, 
      University of Science and Technology of China, Huangshan Road 443, Hefei 230027, 
      Anhui, China.
FAU - Zu, Ya-Nan
AU  - Zu YN
AD  - CAS Key Laboratory of Brain Function and Disease, School of Life Science, 
      University of Science and Technology of China, Huangshan Road 443, Hefei 230027, 
      Anhui, China.
FAU - Zhou, Jiang-Ning
AU  - Zhou JN
AD  - CAS Key Laboratory of Brain Function and Disease, School of Life Science, 
      University of Science and Technology of China, Huangshan Road 443, Hefei 230027, 
      Anhui, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160429
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 9015-71-8 (Corticotropin-Releasing Hormone)
RN  - WI4X0X7BPJ (Hydrocortisone)
SB  - IM
MH  - Animals
MH  - Corticotropin-Releasing Hormone/biosynthesis
MH  - Gene Expression Profiling
MH  - Gene Knock-In Techniques
MH  - HeLa Cells
MH  - Humans
MH  - Hydrocortisone/*metabolism
MH  - *Promoter Regions, Genetic
MH  - *Response Elements
MH  - *Stress, Physiological
MH  - Transcription, Genetic
MH  - Tupaiidae/*physiology
PMC - PMC4850381
EDAT- 2016/04/30 06:00
MHDA- 2018/01/18 06:00
PMCR- 2016/04/29
CRDT- 2016/04/30 06:00
PHST- 2015/12/01 00:00 [received]
PHST- 2016/04/06 00:00 [accepted]
PHST- 2016/04/30 06:00 [entrez]
PHST- 2016/04/30 06:00 [pubmed]
PHST- 2018/01/18 06:00 [medline]
PHST- 2016/04/29 00:00 [pmc-release]
AID - srep24905 [pii]
AID - 10.1038/srep24905 [doi]
PST - epublish
SO  - Sci Rep. 2016 Apr 29;6:24905. doi: 10.1038/srep24905.