ISL1 physically interacts with BETA2 to promote insulin gene transcriptional synergy in non-β cells

ISL1 is a LIM homeodomain protein that plays an important role in insulin gene transcriptional activation and islet cell formation. BETA2 is a transcription factor in the basic helix-loop-helix (bHLH) family, which activates expression of tissue-specific genes in several developmental systems. In this study, we investigated the functional and physical interactions of ISL1 and BETA2 in promoting insulin gene transcription in non-β cells. Using the luciferase assay, we demonstrated that ISL1 and BETA2 could activate insulin gene transcription synergistically. Co-immunoprecipitation also supported that ISL1 and BETA2 appear in one complex and this physical interaction mediates the synergy between these two proteins.