A molecular switch for photoperiod responsiveness in mammals.
Seasonal synchronization based on day length (photoperiod) allows organisms to anticipate environmental change. Photoperiodic decoding relies on circadian clocks, but the underlying molecular pathways have remained elusive [1]. In mammals and birds, photoperiodic responses depend crucially on expression of thyrotrophin β subunit RNA (TSHβ) in the pars tuberalis (PT) of the pituitary gland [2-4]. Now, using our well-characterized Soay sheep model [2], we describe a molecular switch governing TSHβ transcription through the circadian clock. Central to this is a conserved D element in the TSHβ promoter, controlled by the circadian transcription factor thyrotroph embryonic factor (Tef). In the PT, long-day exposure rapidly induces expression of the coactivator eyes absent 3 (Eya3), which synergizes with Tef to maximize TSHβ transcription. The pineal hormone melatonin, secreted nocturnally, sets the phase of rhythmic Eya3 expression in the PT to peak 12 hr after nightfall. Additionally, nocturnal melatonin levels directly suppress Eya3 expression. Together, these effects form a switch triggering a strong morning peak of Eya3 expression under long days. Species variability in the TSHβ D element influences sensitivity to TEF, reflecting species variability in photoperiodic responsiveness. Our findings define a molecular pathway linking the circadian clock to the evolution of seasonal timing in mammals.
Institute of Biological and Environmental Sciences, Zoology Building, Tillydrone Avenue, University of Aberdeen, Aberdeen AB24 2TZ, UK. h.dardente@abdn.ac.uk
Hugues
H
Dardente
Cathy A
CA
Wyse
Mike J
MJ
Birnie
Sandrine M
SM
Dupré
Andrew S I
AS
Loudon
Gerald A
GA
Lincoln
David G
DG
Hazlerigg
D000818:Animals; D001483:Base Sequence; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism; D057906:Circadian Clocks / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008322:Mammals / Q000502:physiology*; D008550:Melatonin / Q000378:metabolism; D008969:Molecular Sequence Data; D017440:Photoperiod; D010902:Pituitary Gland / Q000033:anatomy & histology / Q000502:physiology; D011401:Promoter Regions, Genetic; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism; D012621:Seasons; D016415:Sequence Alignment; D012756:Sheep / Q000502:physiology*; D037322:Thyrotropin, beta Subunit / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D037322:Thyrotropin, beta Subunit; D017027:Protein Tyrosine Phosphatases; D008550:Melatonin