Neuronal PAS domain-containing protein 2 (NPAS2) forms heterodimers which activate E-bo, Xenopus/Amphibian, element (3'-CACGTG-5') transcription of a number of proteins of the circadian clock. This transcription is inhibited in a feedback loop by PER, and also by CRY proteins. NPAS2 is a component of the circadian clock oscillator which includes the CRY proteins, CLOCK or NPAS2, BMAL1 or BMAL2, CSNK1D and/or CSNK1E, TIMELESS and the PER proteins. Efficient DNA binding requires dimerization with another bHLH protein. Heterodimerization with CLOCK or NPAS2 is required for E-bo, Xenopus/Amphibian,-dependent transactivation.