Adrenergic signals direct rhythmic expression of transcriptional repressor CREM in the pineal gland

• Published in: Nature (London) Vol. 365; no. 6444; pp. 314 - 320
• Main Authors: STEHLE, J. H, FOULKES, N. S, MOLINA, C. A, SIMONNEAUX, V, PEVET, P, SASSONE-CORSI, P
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 23.09.1993; Nature Publishing Group
• Subjects: Amino Acid Sequence; Animals; Base Sequence; Biochemistry; Biological and medical sciences; Cells, Cultured; Circadian Rhythm; Circadian rhythms; Cyclic AMP - antagonists & inhibitors; Cyclic AMP - physiology; Cyclic AMP Response Element Modulator; DNA; DNA-Binding Proteins - biosynthesis; DNA-Binding Proteins - genetics; Endocrine system; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation; Hypothalamus. Hypophysis. Epiphysis. Urophysis; Introns; Male; Melatonin - biosynthesis; Molecular Sequence Data; Morphology. Functional localizations; Norepinephrine - physiology; Pineal Gland - physiology; Promoter Regions, Genetic; Rats; Rats, Wistar; Repressor Proteins - biosynthesis; Repressor Proteins - genetics; Suprachiasmatic Nucleus; Sympathetic Nervous System - physiology; Transcription, Genetic; Vertebrates: endocrinology; Molecular form; Endocrine gland; Rat; Rodentia; Central nervous system; Cyclic AMP; Pineal body; Transcription repressor; Circadian rhythm; Gene expression; Signal transduction; Vertebrata; Mammalia; Transcription factor
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/365314a0

Transcription factor CREM appears to play a key physiological and developmental role within the hypothalamic-pituitary-gonadal axis. This axis is modulated by the pineal hormone melatonin, whose production is in turn driven by the endogenous clock. There is striking circadian fluctuation of a novel CREM isoform, ICER, which is expressed at high levels during the night. ICER is generated from an alternative, intronic promoter and functions as a powerful repressor of cyclic AMP-induced transcription. Rhythmic adrenergic signals originated by the clock direct ICER expression by stimulation of the cAMP signal transduction pathway.