High activity of the stress promoter contributes to susceptibility to stress in the tree shrew
| Autor: | Rong-Jun Ni, Ya-Nan Zu, Jiang-Ning Zhou, Yu-Mian Shu, Yun-jun Sun, Qing-Hong Shan, Yu Wang, Yan-Hong Lv, Xiu-Yu Feng, Hui Fang |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty endocrine system Hydrocortisone Transcription Genetic Corticotropin-Releasing Hormone Response element Biology Response Elements Article 03 medical and health sciences Corticotropin-releasing hormone 0302 clinical medicine Glucocorticoid receptor Transcription (biology) Stress Physiological Internal medicine medicine Transcriptional regulation Animals Humans Gene Knock-In Techniques Receptor Promoter Regions Genetic Multidisciplinary Gene Expression Profiling Tupaiidae Gene expression profiling 030104 developmental biology Endocrinology 030217 neurology & neurosurgery hormones hormone substitutes and hormone antagonists medicine.drug HeLa Cells |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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