Down-Regulation of EPAS1 Transcription and Genetic Adaptation of Tibetans to High-Altitude Hypoxia

doi:10.1093/molbev/msw280

	Down-Regulation of EPAS1 Transcription and Genetic Adaptation of Tibetans to High-Altitude Hypoxia
	Peng, Yi 1; Cui, Chaoying 2; He, Yaoxi 1,3; Ouzhuluobu 2; Zhang, Hui 1,2; Yang, Deying 1; Zhang, Qu 4; Bianbazhuoma 5; Yang, Lixin 1; He, Yibo 1,3; Xiang, Kun 1; Zhang, Xiaoming 1; Bhandari, Sushil 1; Shi, Peng 1; Yangla 2; Dejiquzong 2; Baimakangzhuo 2; Duojizhuoma 2; Pan, Yongyue 2; Cirenyangji 2; Baimayangji 2; Gonggalanzi 2; Bai, Caijuan 2; Bianba 2; Basang 6; Ciwangsangbu 6; Xu, Shuhua7,8,9 ; Chen, Hua 10; Liu, Shiming 11; Wu, Tianyi 11; Qi, Xuebin 1; Su, Bing 1,2
	2017-04
发表期刊	MOLECULAR BIOLOGY AND EVOLUTION
ISSN	0737-4038
卷号	34 期号:4 页码:818-830
发表状态	已发表
DOI	10.1093/molbev/msw280
摘要	Tibetans 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.
关键词	high altitude Tibetans hypoxia genetic adaptation EPAS1 transgenic mice
收录类别	SCI
语种	英语
资助项目	Program of Shanghai Academic Research Leader[16XD1404700]
WOS研究方向	Biochemistry & Molecular Biology ; Evolutionary Biology ; Genetics & Heredity
WOS类目	Biochemistry & Molecular Biology ; Evolutionary Biology ; Genetics & Heredity
WOS记录号	WOS:000396762200004
出版者	OXFORD UNIV PRESS
WOS关键词	WHOLE-GENOME ASSOCIATION ; PULMONARY-HYPERTENSION ; POSITIVE SELECTION ; ENDOTHELIAL-CELLS ; OXYGEN-SATURATION ; CONVERTING ENZYME ; INDUCIBLE FACTORS ; BLOOD-PRESSURE ; SEQ ; MICE
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1445
专题	生命科学与技术学院_特聘教授组_徐书华组
通讯作者	Wu, Tianyi; Qi, Xuebin; Su, Bing
作者单位	1.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
推荐引用方式 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.