Identification of Key HIF-1α Target Genes that Regulate Adaptation to Hypoxic Conditions in Tibetan Chicken Embryos

Background: Tibetan chicken, a unique plateau breed, has a suite of adaptive features that enable it to tolerate the high-altitude hypoxic environment. HIF‐1α (hypoxia inducible factor 1 subunit alpha) is a crucial mediator of the cellular response to hypoxia. HIF‐1α maintains oxygen homeostasis by inducing glycolysis, erythropoiesis, and angiogenesis; however, the target genes involved in adaptive responses to hypoxia in animals and birds of plateaus are still unclear. Results: We used ChIP-seq to map HIF‐1α binding regions in chorioallantoic membrane (CAM) tissue of chicken embryos, and identified 752 HIF-1α target genes (TG), of which 112 were differentially expressed target genes (DTGs) between the two breeds. We found that eight genes (PTK2, GPNMB, CALD1, SLC25A1, SPRY2, NUPL2, RANBPL, and CBWD1) play important roles in hypoxic adaption by regulating blood vessel development, energy metabolism through angiogenesis, vascular smooth muscle contraction, and various hypoxia-related signaling pathways (including VEGF and MAPK) in Tibetan chickens during embryonic development. Conclusions: This study enhances our understanding of the molecular mechanisms of hypoxic adaptation in Tibetan chickens and provides new insights into adaptation to hypoxia in humans and other species living at high altitude. Chorioallantoic membrane (CAM) of embryos profiles of 11-day-old Tibetan chickens (TCs) and Chahua chickens (CHs) were generated by deep sequencing, using Illumina HiSeq 2500 platform.