[en] The annual photoperiod cycle provides the critical environmental cue synchronizing rhythms of life in seasonal habitats. In 1936, Bünning proposed a circadian-basis for photoperiodic synchronization. Here, light-dark cycles entrain a circadian rhythm of photosensitivity, and the expression of summer or winter biology depends on whether light coincides with the phase of high photosensitivity. Formal studies support the universality of this so-called coincidence timer, but we lack understanding of the mechanisms involved. Here we show in mammals that coincidence timing takes place in the pars tuberalis of the pituitary, through a melatonin-dependent flip-flop switch between circadian transcriptional activation and repression. Long photoperiods produce short night-time melatonin signals, leading to induction of the circadian transcription factor BMAL2, in turn triggering summer biology through the eyes absent / thyrotrophin (EYA3 / TSH) pathway. Conversely, short photoperiods produce long melatonin signals, inducing circadian repressors including DEC1, in turn suppressing BMAL2 and the EYA3/TSH pathway, triggering winter biology. These actions are associated with progressive genome-wide changes in chromatin state, elaborating the effect of the circadian coincidence timer. Hence, circadian clock interactions with pituitary epigenetic pathways form the basis of the mammalian coincidence timer mechanism. Our results constitute a blueprint for circadian-based seasonal timekeeping in vertebrates.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Wood, S.H. ✱; University of Manchester > Faculty of Life Sciences > Centre for Biological Timing
Hindle, M.M. ✱; University of Edinburgh > The Roslin Institute
Mizoro, Yasutaka ; University of Manchester > Faculty of Life Sciences > Centre for Biological Timing
Cheng, Y; The University of Queensland > UQ Genomics Initiative
Saer, B.R.C.; University of Manchester > Faculty of Life Sciences > Centre for Biological Timing
Miedzinska, K; University of Edinburgh > The Roslin Institute
Christian, H.C.; University of Oxford > Department of Physiology, Anatomy and Genetics
Begley, N.; University of Manchester > Faculty of Life Sciences > Centre for Biological Timing
McNeilly, J.; Queen's Medical Research Institute > MRC Centre for Reproductive Health
McNeilly, A.S.; Queen's Medical Research Institute > MRC Centre for Reproductive Health
Meddle, S.L.; University of Edinburgh > The Roslin Institute
Burt, D.W.; The University of Queensland > UQ Genomics Initiative
Loudon, A.S.I.; University of Manchester > Faculty of Life Sciences > Centre for Biological Timing
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