Down-Regulation of EPAS1 Transcription and Genetic Adaptation of Tibetans to High-Altitude Hypoxia
Peng, Yi1; Cui, Chaoying2; He, Yaoxi1,3; Ouzhuluobu2; Zhang, Hui1,2; Yang, Deying1; Zhang, Qu4; Bianbazhuoma5; Yang, Lixin1; He, Yibo1,3; Xiang, Kun1; Zhang, Xiaoming1; Bhandari, Sushil1; Shi, Peng1; Yangla2; Dejiquzong2; Baimakangzhuo2; Duojizhuoma2; Pan, Yongyue2; Cirenyangji2; Baimayangji2; Gonggalanzi2; Bai, Caijuan2; Bianba2; Basang6; Ciwangsangbu6; Xu, Shuhua7,8,9; Chen, Hua10; Liu, Shiming11; Wu, Tianyi11; Qi, Xuebin1; Su, Bing1,2
2017-04
Source PublicationMOLECULAR BIOLOGY AND EVOLUTION
ISSN0737-4038
Volume34Issue:4Pages:818-830
Status已发表
DOI10.1093/molbev/msw280
AbstractTibetans are well adapted to the hypoxic environments at high altitude, yet the molecular mechanism of this adaptation remains elusive. We reported comprehensive genetic and functional analyses of EPAS1, a gene encoding hypoxia inducible factor 2 alpha ( HIF-2 alpha) with the strongest signal of selection in previous genome-wide scans of Tibetans. We showed that the Tibetan-enriched EPAS1 variants down-regulate expression in human umbilical endothelial cells and placentas. Heterozygous EPAS1 knockout mice display blunted physiological responses to chronic hypoxia, mirroring the situation in Tibetans. Furthermore, we found that the Tibetan version of EPAS1 is not only associated with the relatively low hemoglobin level as a polycythemia protectant, but also is associated with a low pulmonary vasoconstriction response in Tibetans. We propose that the down-regulation of EPAS1 contributes to the molecular basis of Tibetans' adaption to high-altitude hypoxia.
Keywordhigh altitude Tibetans hypoxia genetic adaptation EPAS1 transgenic mice
Indexed BySCI
Language英语
Funding ProjectProgram of Shanghai Academic Research Leader[16XD1404700]
WOS Research AreaBiochemistry & Molecular Biology ; Evolutionary Biology ; Genetics & Heredity
WOS SubjectBiochemistry & Molecular Biology ; Evolutionary Biology ; Genetics & Heredity
WOS IDWOS:000396762200004
PublisherOXFORD UNIV PRESS
WOS KeywordWHOLE-GENOME ASSOCIATION ; PULMONARY-HYPERTENSION ; POSITIVE SELECTION ; ENDOTHELIAL-CELLS ; OXYGEN-SATURATION ; CONVERTING ENZYME ; INDUCIBLE FACTORS ; BLOOD-PRESSURE ; SEQ ; MICE
Original Document TypeArticle
Citation statistics
Cited Times:51[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttps://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1445
Collection生命科学与技术学院_特聘教授组_徐书华组
Corresponding AuthorWu, Tianyi; Qi, Xuebin; Su, Bing
Affiliation1.Chinese Acad Sci, Kunming Inst Zool, State Key Lab Genet Resources & Evolut, Kunming, Peoples R China
2.Tibetan Univ, Sch Med, High Altitude Med Res Ctr, Lhasa, Peoples R China
3.Univ Chinese Acad Sci, Kunming Coll Life Sci, Beijing, Peoples R China
4.Perspect Sci, Chongqing, Peoples R China
5.Municipal Peoples Hosp Lhasa, Lhasa, Peoples R China
6.Peoples Hosp Dangxiong Cty, Dangxiong, Peoples R China
7.Chinese Acad Sci, Shanghai Inst Biol Sci, Max Planck Independent Res Grp Populat Gen, CAS MPG Partner Inst Computat Biol PICB,Key Lab C, Shanghai, Peoples R China
8.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China
9.Collaborat Innovat Ctr Genet & Dev, Shanghai, Peoples R China
10.Chinese Acad Sci, Beijing Inst Genom, Ctr Computat Genom, Beijing, Peoples R China
11.High Altitude Med Res Inst, Natl Key Lab High Altitude Med, Xining, Peoples R China
Recommended Citation
GB/T 7714
Peng, Yi,Cui, Chaoying,He, Yaoxi,et al. Down-Regulation of EPAS1 Transcription and Genetic Adaptation of Tibetans to High-Altitude Hypoxia[J]. MOLECULAR BIOLOGY AND EVOLUTION,2017,34(4):818-830.
APA Peng, Yi.,Cui, Chaoying.,He, Yaoxi.,Ouzhuluobu.,Zhang, Hui.,...&Su, Bing.(2017).Down-Regulation of EPAS1 Transcription and Genetic Adaptation of Tibetans to High-Altitude Hypoxia.MOLECULAR BIOLOGY AND EVOLUTION,34(4),818-830.
MLA Peng, Yi,et al."Down-Regulation of EPAS1 Transcription and Genetic Adaptation of Tibetans to High-Altitude Hypoxia".MOLECULAR BIOLOGY AND EVOLUTION 34.4(2017):818-830.
Files in This Item: Download All
File Name/Size DocType Version Access License
10.1093@molbev@msw28(810KB)期刊论文出版稿开放获取implied-oaView Download
Related Services
Usage statistics
Scholar Google
Similar articles in Scholar Google
[Peng, Yi]'s Articles
[Cui, Chaoying]'s Articles
[He, Yaoxi]'s Articles
Baidu academic
Similar articles in Baidu academic
[Peng, Yi]'s Articles
[Cui, Chaoying]'s Articles
[He, Yaoxi]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Peng, Yi]'s Articles
[Cui, Chaoying]'s Articles
[He, Yaoxi]'s Articles
Terms of Use
No data!
Social Bookmark/Share
File name: 10.1093@molbev@msw280.pdf
Format: Adobe PDF
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.