KMS Of Academy of mathematics and systems sciences, CAS
| Chromatin accessibility landscape and regulatory network of high-altitude hypoxia adaptation | |
Xin, Jingxue1,2,3,4,5; Zhang, Hui1,3; He, Yaoxi1,3,5; Duren, Zhana6,11,12; Bai, Caijuan7; Chen, Lang2,5; Luo, Xin1,3,5; Yan, Dong-Sheng8; Zhang, Chaoyu2,5; Zhu, Xiang6; Yuan, Qiuyue2,5; Feng, Zhanying2,5; Cui, Chaoying7; Qi, Xuebin1,3; Ouzhuluobu7; Wong, Wing Hung4,6,9; Wang, Yong2,3,5,10 ; Su, Bing1,3
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| 2020-10-01 | |
| Source Publication | NATURE COMMUNICATIONS
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| ISSN | 2041-1723 |
| Volume | 11Issue:1Pages:20 |
| Abstract | 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. |
| DOI | 10.1038/s41467-020-18638-8 |
| Indexed By | SCI |
| Language | 英语 |
| Funding Project | 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 Research Area | Science & Technology - Other Topics |
| WOS Subject | Multidisciplinary Sciences |
| WOS ID | WOS:000577113300008 |
| Publisher | NATURE RESEARCH |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | http://ir.amss.ac.cn/handle/2S8OKBNM/52359 |
| Collection | 应用数学研究所 |
| Corresponding Author | Wong, Wing Hung; Wang, Yong; Su, Bing |
| Affiliation | 1.Chinese Acad Sci, Kunming Inst Zool, State Key Lab Genet Resources & Evolut, Kunming 650223, Yunnan, Peoples R China 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 11.Clemson Univ, Ctr Human Genet, Greenwood, SC 29646 USA 12.Clemson Univ, Dept Biochem & Genet, Greenwood, SC 29646 USA |
| Recommended Citation 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. |
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