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. Efficient DNA-binding requires dimerization with another bHLH protein (PubMed:12810726, PubMed:18069799). Heterodimer with TCF3/E47; the heterodimer is inhibited in presence of ID2, but not NR0B2, to E-box element (PubMed:18069799, PubMed:23395635). Interacts with EP300; the interaction is inhibited by NR0B2 (PubMed:9512516). Interacts with RREB1 (By similarity). Interacts with ATOH8 (PubMed:18560595). In pancreatic islet cells, shuttles to the nucleus in response to glucose stimulation. Colocalizes with NR0B2 in the nucleus (By similarity). Expressed in pancreatic beta cells, pulmonary neuroendocrine cells and retinal interneurons amacrine cells (at protein level). Expressed in endocrine cells of the pancreas. Expressed in the inner layer of cerebellar external granular layer (EGL). Expressed in the Ammon's horn (AH), which includes the CA1-CA3 pyramidal layer and in granule cells of the dentate gyrus (DG). Expressed in photoreceptors of the outer nuclear layer (ONL), in a subset of cells in the lower half of the inner nuclear layer (INL), and in a subset of cells in the ganglion cell layer (GCL) of the retina. Expressed in cholinergic and AII amacrine cell types. Expressed in differentiating neurons of both the central and peripheral nervous systems. Expressed in glucagon- and ghrelin-producing cells of the pancreas at 14.5 dpc. Expressed in each of the hormone-producing cells population of the pancreas, except somatostatin-producing cells at 16.5 dpc (at protein level). Expressed during embryonic development. Expressed in the earliest islet precursor cells of the pancreas at 9.5 dpc. Expressed in neuronal cells in the inner ear between 9.5 and 12.5 dpc. Expressed within the otic epithelium and among the delaminating cells migrating away from the ear to form sensory neurons at 10.5 dpc. Expressed in the upper blade of the nascent dentate gyrus at 16.5 dpc. Up-regulated by NKX2-2 and NEUROG3. In islet cells, phosphorylated on Ser-274 upon glucose stimulation; which may be required for nuclear localization. In activated neurons, phosphorylated on Ser-336; which promotes dendritic growth (By similarity). Phosphorylated by MAPK1; phosphorylation regulates heterodimerization and DNA-binding activities. Phosphorylation on Ser-266 and Ser-274 increases transactivation on the insulin promoter in glucose-stimulated insulinoma cells. Mice are deaf and die shortly after birth due to neonatal diabetes that results from developmental and functional defects of the pancreatic endocrine cells. Show a loss of enteroendocrine cells in the small intestine, airway and alveolar epithelial cells in the lung, granular neuronal cells in the cerebellum, hippocampal dentate gyrus and sensory neurons in the inner ear due to extensive cell death that occurs during the early stages of differentiation.