Rhythmic transcription: The molecular basis of circadian melatonin synthesis

Rhythmic transcription: The molecular basis of circadian melatonin synthesis Adaptation to a changing environment is an essential feature of physiological regulation. The day/night rhythm is translated into hormonal oscillations governing the physiology of all living organisms. In mammals the pineal gland is responsible for the synthesis of the hormone melatonin in response to signals originating from the endogenous clock located in the hypothalamic suprachiasmatic nucleus (SCN). The molecular mechanisms involved in rhythmic synthesis of melatonin involve the CREM gene, which encodes transcription factors responsive to activation of the cAMP signalling pathway. The CREM product, ICER, is rhythmically expressed and participates in a transcriptional autoregulatory loop which also controls the amplitude of oscillations of serotonin N‐acetyl transferase (AANAT), the rate‐limiting enzyme of melatonin synthesis. In contrast, chick pinealocytes possess an endogenous circadian pacemaker which directs AANAT rhythmic expression. cAMP‐responsive activator transcription factors CREB and ATF1 and the repressor ICER are highly conserved in the chick with the notable exception of ATF1 that possesses two glutamine‐rich domains in contrast to the single domain encountered to date in mammalian systems. ICER is cAMP inducible and undergoes a characteristic day‐night oscillation in expression reminiscent of AA‐NAT, but with a peak towards the end of the night. Interestingly CREB appears to be phosphorylated constitutively with a transient fall occurring at the beginning of the night. Thus, a transcription factor modulates the oscillatory levels of a hormone. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Biology of the Cell Wiley

Rhythmic transcription: The molecular basis of circadian melatonin synthesis

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Publisher
Wiley
Copyright
1997 Société Française des Microscopies and Société Biologie Cellulaire de France
ISSN
0248-4900
eISSN
1768-322X
DOI
10.1016/S0248-4900(98)80004-X
Publisher site
See Article on Publisher Site

Abstract

Adaptation to a changing environment is an essential feature of physiological regulation. The day/night rhythm is translated into hormonal oscillations governing the physiology of all living organisms. In mammals the pineal gland is responsible for the synthesis of the hormone melatonin in response to signals originating from the endogenous clock located in the hypothalamic suprachiasmatic nucleus (SCN). The molecular mechanisms involved in rhythmic synthesis of melatonin involve the CREM gene, which encodes transcription factors responsive to activation of the cAMP signalling pathway. The CREM product, ICER, is rhythmically expressed and participates in a transcriptional autoregulatory loop which also controls the amplitude of oscillations of serotonin N‐acetyl transferase (AANAT), the rate‐limiting enzyme of melatonin synthesis. In contrast, chick pinealocytes possess an endogenous circadian pacemaker which directs AANAT rhythmic expression. cAMP‐responsive activator transcription factors CREB and ATF1 and the repressor ICER are highly conserved in the chick with the notable exception of ATF1 that possesses two glutamine‐rich domains in contrast to the single domain encountered to date in mammalian systems. ICER is cAMP inducible and undergoes a characteristic day‐night oscillation in expression reminiscent of AA‐NAT, but with a peak towards the end of the night. Interestingly CREB appears to be phosphorylated constitutively with a transient fall occurring at the beginning of the night. Thus, a transcription factor modulates the oscillatory levels of a hormone.

Journal

Biology of the CellWiley

Published: Nov 1, 1997

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