Transcriptional regulation of the hypocretin/orexin gene.

The hypocretin (also known as orexin) system reacts to environmental changes in the internal milieu (pH, glucose, and various hormones) and the external environment (activity, fasting, and sleep deprivation) and regulates various physiological functions. Several feedback mechanisms, such as those listed above, have been reported to regulate the hypocretin system even at the transcriptional level. In addition, some transcription factors, such as forkhead box A2; nuclear receptor subfamily 6, group A, member 1; and early B-cell factor 2, were determined to be regulators of the preprohypocretin gene. However, little is known concerning the specific components that react to environmental changes and the determinants of spatial expression of the hypocretin gene within the lateral hypothalamus. This review focuses on the recent findings of transcription factors that regulate preprohypocretin transcription in addition to discussing the future prospects for transcriptional regulation of the hypocretin gene.