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
F. Guillaumond et al., 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, J NEUROCHEM, 75(4), 2000, pp. 1398-1407
The daily rhythm in circulating melatonin is driven by a circadian rhythm i
n 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 be
lieved to involve inhibitory transcription factors, among which Fos-related
antigen 2 (Fra-2) appears as a good candidate, Circadian rhythms in the ex
pression 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 variatio
ns in AP-1 binding activity. Quantitative variations in the Fra-2 component
over the circadian cycle were associated with qualitative variations in pr
otein isoforms, Destruction of the suprachiasmatic nucleus resulted in decr
eased nocturnal AP-1 activity, showing that AP-1 circadian rhythm is driven
by this nucleus. Exposure to light during subjective night and administrat
ion of a serotonin 5-HT1A/5-HT7 receptor agonist during subjective day, res
pectively, 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 suprachi
asmatic nucleus according to a "phase dependence" that is characteristic of
the rhythm of clock sensitivity to both zeitgebers.