Acts as a transcriptional activator: mediates transcriptional activation by binding to E box-containing promoter consensus core sequences 5'-CANNTG-3'. Associates with the p300/CBP transcription coactivator complex to stimulate transcription of the secretin gene as well as the gene encoding the cyclin-dependent kinase inhibitor CDKN1A. Contributes to the regulation of several cell differentiation pathways, like those that promote the formation of early retinal ganglion cells, inner ear sensory neurons, granule cells forming either the cerebellum or the dentate gyrus cell layer of the hippocampus, endocrine islet cells of the pancreas and enteroendocrine cells of the small intestine. Together with PAX6 or SIX3, is required for the regulation of amacrine cell fate specification. Also required for dendrite morphogenesis and maintenance in the cerebellar cortex. Associates with chromatin to enhancer regulatory elements in genes encoding key transcriptional regulators of neurogenesis (By similarity). Efficient DNA-binding requires dimerization with another bHLH protein. Heterodimer with TCF3/E47; the heterodimer is inhibited in presence of ID2, but not NR0B2, to E-box element. Interacts with EP300; the interaction is inhibited by NR0B2 (By similarity). Interacts with RREB1 (PubMed:12482979). Interacts with ATOH8 (By similarity). In pancreatic islet cells, shuttles to the nucleus in response to glucose stimulation. Colocalizes with NR0B2 in the nucleus (By similarity). Most abundant in pancreatic alpha- and beta-cells, less in brain and intestine. Phosphorylated. In islet cells, phosphorylated on Ser-273 upon glucose stimulation; which may be required for nuclear localization. In activated neurons, phosphorylated on Ser-334; which promotes dendritic growth. Phosphorylated by MAPK1; phosphorylation regulates heterodimerization and DNA-binding activities. Phosphorylation on Ser-265 and Ser-273 increases transactivation on the insulin promoter in glucose-stimulated insulinoma cells (By similarity). Extended N-terminus.