Chromatin accessibility landscape and regulatory network of high-altitude hypoxia adaptation
| Autor: | Xin Luo, Jingxue Xin, Xuebin Qi, Zhanying Feng, Hui Zhang, Qiuyue Yuan, Wing Hung Wong, Yaoxi He, Lang Chen, Zhana Duren, Caijuan Bai, Yong Wang, Chaoyu Zhang, Ouzhuluobu, Dong Sheng Yan, Xiang Zhu, Chaoying Cui, Bing Su |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Acclimatization Gene regulatory network General Physics and Astronomy Evolutionary biology RNA-Seq Altitude Sickness Tibet 0302 clinical medicine Pregnancy Basic Helix-Loop-Helix Transcription Factors Ethnicity Gene Regulatory Networks Regulatory Elements Transcriptional Hypoxia lcsh:Science Cells Cultured Disease Resistance Regulation of gene expression Multidisciplinary Natural selection Altitude EPAS1 Genomics Chromatin Cell Hypoxia Chromatin Immunoprecipitation Sequencing Data integration Female Cell type Science Primary Cell Culture Computational biology Biology Polymorphism Single Nucleotide Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Human Umbilical Vein Endothelial Cells Humans Selection Genetic Gene Models Genetic Whole Genome Sequencing General Chemistry Gene regulation Oxygen 030104 developmental biology Gene Expression Regulation lcsh:Q 030217 neurology & neurosurgery Transcription Factors |
| Zdroj: | Nature Communications, Vol 11, Iss 1, Pp 1-20 (2020) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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