Chromatin accessibility landscape and regulatory network of high-altitude hypoxia adaptation

doi:10.1038/s41467-020-18638-8

CORC > 数学与系统科学研究院 > 中国科学院数学与系统科学研究院 > 应用数学研究所

	Chromatin accessibility landscape and regulatory network of high-altitude hypoxia adaptation
	Xin, Jingxue 2,3,4,5,11; Zhang, Hui 3,11; He, Yaoxi 3,5,11; Duren, Zhana 1,6,12; Bai, Caijuan 7; Chen, Lang 2,5; Luo, Xin 3,5,11; Yan, Dong-Sheng 8; Zhang, Chaoyu 2,5; Zhu, Xiang 6
刊名	NATURE COMMUNICATIONS
	2020-10-01
卷号	11 期号:1 页码:20
ISSN号	2041-1723
DOI	10.1038/s41467-020-18638-8
英文摘要	High-altitude adaptation of Tibetans represents a remarkable case of natural selection during recent human evolution. Previous genome-wide scans found many non-coding variants under selection, suggesting a pressing need to understand the functional role of non-coding regulatory elements (REs). Here, we generate time courses of paired ATAC-seq and RNA-seq data on cultured HUVECs under hypoxic and normoxic conditions. We further develop a variant interpretation methodology (vPECA) to identify active selected REs (ASREs) and associated regulatory network. We discover three causal SNPs of EPAS1, the key adaptive gene for Tibetans. These SNPs decrease the accessibility of ASREs with weakened binding strength of relevant TFs, and cooperatively down-regulate EPAS1 expression. We further construct the downstream network of EPAS1, elucidating its roles in hypoxic response and angiogenesis. Collectively, we provide a systematic approach to interpret phenotype-associated noncoding variants in proper cell types and relevant dynamic conditions, to model their impact on gene regulation. Tibetan adaptation to the high-altitude environment represents a case of natural selection during recent human evolution. Here the authors investigated the chromatin and transcriptional landscape of umbilical endothelial cells from Tibetan and Han Chinese donors and provide genome-wide characterization of the hypoxia regulatory network associated high-altitude adaptation.
资助项目	National Natural Science Foundation of China (NSFC)[91631306] ; Strategic Priority Research Program of the Chinese Academy of Sciences (CAS)[XDA20040102] ; Strategic Priority Research Program of the Chinese Academy of Sciences (CAS)[XDB13000000] ; NSFC[11871463] ; NSFC[61671444] ; NSFC[61621003] ; NSFC[31660308] ; Youth Innovation Promotion Association of CAS ; State Key Laboratory of Genetic Resources and Evolution[GREKF1807] ; Shanghai Municipal Science and Technology Major Project[2017SHZDZX01] ; Natural Science Foundation of Yunnan Province[2019FB042] ; NIH[P50HG007735] ; NIH[R01GM109836] ; NIH[R01HG010359]
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	NATURE RESEARCH
WOS记录号	WOS:000577113300008
内容类型	期刊论文
源URL	[http://ir.amss.ac.cn/handle/2S8OKBNM/52358]
专题	应用数学研究所
通讯作者	Wong, Wing Hung; Wang, Yong; Su, Bing
作者单位	1.Clemson Univ, Ctr Human Genet, Greenwood, SC 29646 USA 2.Chinese Acad Sci, Acad Math & Syst Sci, CEMS, NCMIS,MDIS, Beijing 100190, Peoples R China 3.Chinese Acad Sci, Ctr Excellence Anim Evolut & Genet, Kunming 650223, Yunnan, Peoples R China 4.Stanford Univ, BioX Program, Stanford, CA 94305 USA 5.Univ Chinese Acad Sci, Beijing 100101, Peoples R China 6.Stanford Univ, Dept Stat, Stanford, CA 94305 USA 7.Tibetan Univ, Sch Med, High Altitude Med Res Ctr, Lhasa 850000, Peoples R China 8.Inner Mongolia Univ, Sch Math Sci, Hohhot 010021, Peoples R China 9.Stanford Univ, Sch Med, Dept Biomed Data Sci, Stanford, CA 94305 USA 10.Univ Chinese Acad Sci, Chinese Acad Sci, Hangzhou Inst Adv Study, Key Lab Syst Biol, Hangzhou 330106, Peoples R China
推荐引用方式 GB/T 7714	Xin, Jingxue,Zhang, Hui,He, Yaoxi,et al. Chromatin accessibility landscape and regulatory network of high-altitude hypoxia adaptation[J]. NATURE COMMUNICATIONS,2020,11(1):20.
APA	Xin, Jingxue.,Zhang, Hui.,He, Yaoxi.,Duren, Zhana.,Bai, Caijuan.,...&Su, Bing.(2020).Chromatin accessibility landscape and regulatory network of high-altitude hypoxia adaptation.NATURE COMMUNICATIONS,11(1),20.
MLA	Xin, Jingxue,et al."Chromatin accessibility landscape and regulatory network of high-altitude hypoxia adaptation".NATURE COMMUNICATIONS 11.1(2020):20.