KLF4, a Key Regulator of a Transitive Triplet, Acts on the TGF-? Signaling Pathway and Contributes to High-Altitude Adaptation of Tibetan Pigs

Tibetan pigs are native mammalian species on the Plateau that have evolved distinct physiological traits allow them to tolerate high-altitude hypoxic environments. However, genetic mechanism underlying this adaptation remains elusive. Here, based multitissue transcriptional data from and low-altitude Rongchang pigs, we performed a weighted correlation network analysis (WGCNA) identified key modules related these tissues. Complex bioinformatics were integrated identify genes three-node motifs. We found among six tissues (muscle, liver, heart, spleen, kidneys, lungs), lung tissue may be organs for adapt environment. In of KLF4 , BCL6B EGR1 EPAS1 SMAD6 SMAD7 KDR ATOH8 CCN1 as potential regulators hypoxia adaption. might simultaneously regulate gene, forming KLF4–EGR1–BCL6B complex. This complex, dominated by enhance tolerance mediating TGF-? signaling pathway. The complex also affect PI3K-Akt pathway, which plays an important role in angiogenesis caused hypoxia. Therefore, postulate beneficial survive better Although further molecular experiments independent large-scale studies needed verify our findings, findings provide new details regulatory architecture hypoxia-adaptive valuable understanding mammals.