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Here we use sheep as an animal model for low-to-high altitude translocation. We generate multi-omics data including whole-genome sequences, time-resolved bulk RNA-Seq, ATAC-Seq and single-cell RNA-Seq from multiple tissues as well as phenotypic data from 20 bio-indicators. We characterize transcriptional changes of all genes in each tissue, and examine multi-tissue temporal dynamics and transcriptional interactions among genes. Particularly, we identify critical functional genes regulating the short response to hypoxia in each tissue (e.g.,\n                    <jats:italic>PARG<\/jats:italic>\n                    in the cerebellum and\n                    <jats:italic>HMOX1<\/jats:italic>\n                    in the colon). We further identify TAD-constrained\n                    <jats:italic>cis<\/jats:italic>\n                    -regulatory elements, which suppress the transcriptional activity of most genes under hypoxia. Phenotypic and transcriptional evidence indicate that antenatal hypoxia could improve hypoxia tolerance in offspring. Furthermore, we provide time-series expression data of candidate genes associated with human mountain sickness (e.g.,\n                    <jats:italic>BMPR2<\/jats:italic>\n                    ) and high-altitude adaptation (e.g.,\n                    <jats:italic>HIF1A<\/jats:italic>\n                    ). Our study provides valuable resources and insights for future hypoxia-related studies in mammals.\n                  <\/jats:p>","DOI":"10.1038\/s41467-024-48261-w","type":"journal-article","created":{"date-parts":[[2024,5,10]],"date-time":"2024-05-10T14:02:25Z","timestamp":1715349745000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["A time-resolved multi-omics atlas of transcriptional regulation in response to high-altitude hypoxia across whole-body tissues"],"prefix":"10.1038","volume":"15","author":[{"given":"Ze","family":"Yan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Tian","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Liang","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Xin","family":"Mo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei-Ming","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Hui","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Jing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6013-2262","authenticated-orcid":false,"given":"Feng-Hua","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5194-2506","authenticated-orcid":false,"given":"Meng-Hua","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,10]]},"reference":[{"key":"48261_CR1","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1146\/annurev-pathol-012513-104720","volume":"9","author":"GL Semenza","year":"2014","unstructured":"Semenza, G. 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