Circadian clock mechanism driving mammalian photoperiodism

S H Wood,Y Mizoro,Y Cheng,B R C Saer,S L Meddle,D W Burt,N Begley,J Mcneilly,H C Christian,A S Mcneilly,A S I Loudon,M M Hindle,K Miedzinska

doi:10.1038/s41467-020-18061-z

Abstract

The annual photoperiod cycle provides the critical environmental cue synchronizing rhythms of life in seasonal habitats. In 1936, Bünning proposed a circadian-based coincidence timer for photoperiodic synchronization in plants. 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 long photoperiods induce the circadian transcription factor BMAL2, in the pars tuberalis of the pituitary, and triggers summer biology through the eyes absent/thyrotrophin (EYA3/TSH) pathway. Conversely, long-duration melatonin signals on short photoperiods induce circadian repressors including DEC1, 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-pituitary epigenetic pathway interactions form the basis of the mammalian coincidence timer mechanism. Our results constitute a blueprint for circadian-based seasonal timekeeping in vertebrates.

Highlights

The annual photoperiod cycle provides the critical environmental cue synchronizing rhythms of life in seasonal habitats
Using a study design that compared the effects of transfer from long photoperiod (LP) to short photoperiod (SP) with transfer from SP to LP (Fig. 1b), we collected pars tuberalis (PT) tissue at 1,7 and 28 days after transfer, with collections timed for 4-h after lights on (ZT4), when EYA3 expression peaks under LP22,24,29
Comparing LP day 28 to SP day 28 by electron microscopy we found an increased nuclear diameter, equating to an approximate doubling in volume of PT thyrotrophs, and a marked reduction in chromatin density on LP (Fig. 1c, Supplementary Fig. 1e, f)

Summary

Introduction

The annual photoperiod cycle provides the critical environmental cue synchronizing rhythms of life in seasonal habitats. Long-duration melatonin signals on short photoperiods induce circadian repressors including DEC1, 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. EYA3 co-activates the PAR bZIP Transcription Factor TEF (thyrotroph embryonic factor) via a Dbox element on the TSHβ promoter[22,23,24] (Fig. 1a) This prior work places EYA3 at the center of photoperiodic time measurement within the melatonin target tissue, but does not explain how expression is regulated by the seasonal clockwork. Circadian clock interactions with pituitary epigenetic pathways form the basis of the mammalian coincidence timer mechanism

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Results

Conclusion