Circadian binding activity of AP-1, a regulator of the arylalkylamine N-acetyltransferase gene in the rat pineal gland, depends on circadian Fra-2, c-Jun, and Jun-D expression and is regulated by the clock's zeitgebers.
The daily rhythm in circulating melatonin is driven by a circadian rhythm in the expression of the arylalkylamine N:-acetyltransferase gene in the rat pineal gland. Turning off expression of this gene at the end of night is believed to involve inhibitory transcription factors, among which Fos-related antigen 2 (Fra-2) appears as a good candidate. Circadian rhythms in the expression of three proteins of activating protein-1 (AP-1) complexes, namely, Fra-2, c-Jun, and Jun-D, are shown here to account for circadian variations in AP-1 binding activity. Quantitative variations in the Fra-2 component over the circadian cycle were associated with qualitative variations in protein isoforms. Destruction of the suprachiasmatic nucleus resulted in decreased nocturnal AP-1 activity, showing that AP-1 circadian rhythm is driven by this nucleus. Exposure to light during subjective night and administration of a serotonin 5-HT(1A)/5-HT(7) receptor agonist during subjective day, respectively, induced a 50% decrease and a 50% increase in both AP-1 and Fra-2 expression. These effects were impaired by suprachiasmatic nucleus lesions. These data show that pineal AP-1 binding activity, which results from Fra-2 expression, can be modulated by light and serotonin through the suprachiasmatic nucleus according to a "phase dependence" that is characteristic of the rhythm of clock sensitivity to both zeitgebers.
Guillaumond
F
F
INSERM U501, Institut Fédératif Jean-Roche, Faculté de Médecine Nord, Université de la Méditerranée, Marseille, France.
Sage
D
D
Deprez
P
P
Bosler
O
O
Becquet
D
D
François-Bellan
A M
AM
D000704:Analysis of Variance; D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D001683:Biological Clocks / Q000502:physiology*; D002940:Circadian Rhythm / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D003624:Darkness; D051921:Fos-Related Antigen-2; D008027:Light; D008297:Male; D008550:Melatonin / Q000378:metabolism; D010870:Pineal Gland / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology; D013493:Suprachiasmatic Nucleus / Q000502:physiology / Q000601:surgery; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis
D004268:DNA-Binding Proteins; D051921:Fos-Related Antigen-2; C497874:Fosl2 protein, rat; D020033:Protein Isoforms; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D012701:Serotonin; D001191:Arylamine N-Acetyltransferase; D008550:Melatonin