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 <i>UCP1</i> gene, a key regulator of thermogenesis, by comparing its promoter with those of <i>UCP2</i> and <i>UCP3</i> 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-<i>UCP1</i> 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 <i>UCP1</i> and <i>UCP2</i> promoters than between the <i>UCP1</i> orthologs. While some REs (e.g., EN1, POU6F1, and TEAD4) were <i>UCP1</i>-specific, others (e.g., PPARG and RXR) were shared by all <i>UCP</i>s. These results reveal conserved and species-specific regulatory patterns that contribute to the understanding of the transcriptional control of thermogenesis in human adipocytes.