In silico analysis of UCP promoters predicts conserved and human specific regulators of adipocyte thermogenesis.

Adipocyte thermogenesis is a promising therapeutic target to treat metabolic diseases. We predicted transcription factors (TFs) and response elements (REs) regulating the human UCP1 gene, a key regulator of thermogenesis, by comparing its promoter with those of UCP2 and UCP3 in humans, mice, and rats. Using the Eukaryotic Promoter Database, we identified conserved and human-specific TF-REs and developed a scoring system based on RE frequency and TF-UCP1 co-expression in human neck adipocytes. Additional databases refined the list of potential regulators. Transposable elements and base substitutions partially explained sequence divergence between species, and RE analysis revealed greater similarity between the human UCP1 and UCP2 promoters than between the UCP1 orthologs. While some REs (e.g., EN1, POU6F1, and TEAD4) were UCP1-specific, others (e.g., PPARG and RXR) were shared by all UCPs. These results reveal conserved and species-specific regulatory patterns that contribute to the understanding of the transcriptional control of thermogenesis in human adipocytes.