DNA methylation is a widespread mechanism of light-induced circadian clock period plasticity

Abstract

The suprachiasmatic nucleus (SCN) of the hypothalamus is a principal light-responsive circadian clock that adjusts circadian rhythms in mammalian physiology and behavior to changes in external light signals. Although mechanisms underlying how light acutely resets the timing of circadian rhythms have been characterized, it remains elusive how light signals induce lasting changes in circadian period, so-called period after-effects. Here we have found that the period after-effects on circadian behavior of changing photoperiods are blocked by application of DNA methyltransferase inhibitors directed to the SCN. At the level of single light pulses that act as clock-resetting stimulations, pharmacologically inhibiting DNA methylation in the SCN significantly attenuates period after-effects following acute phase shifts in behavioral rhythms in vivo, and blocks period after-effects on clock gene rhythms in the isolated ex vivo SCN. Acute clock resetting shifts themselves, however, do not appear to require DNA methylation at the SCN and behavioral levels, in contrast to subsequent period plasticity. Our results indicate that DNA methylation in the SCN mediates light-induced period after-effects in response to photoperiods, and single light pulses, and together with previous studies showing that DNA methylation in the SCN is essential for period after-effects of non-24hr light cycles (T-cycles), suggest that DNA methylation in the SCN is a widespread mechanism of light-induced circadian period plasticity.