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A Molecular Switch for Photoperiod Responsiveness in Mammals
Open accessAbstract
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.
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“In the sheep pars tuberalis, transcript levels of the transcription factor Eyes absent 3 (Eya3) are controlled both by a circadian signal (that licenses eya3 transcription 12 h after night fall) and by the acute levels of melatonin (that lead to a suppression of eya3 transcription during darkness).”
From An Overview of Monthly Rhythms and Clocks (2017) · cites this paper as [56]
In the citing paper
“As melatonin levels are suppressed by light, the combination of these regulatory mechanisms leads to a specific upregulation of eya3 only under short photoperiod (56).”
From An Overview of Monthly Rhythms and Clocks (2017) · cites this paper as [56]
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Metadata
- Authors
- Dardente, H., Wyse, C. A., Birnie, M. J., Dupré, S. M., Loudon, A. S. I., Lincoln, G. A., & Hazlerigg, D. G.
- Affiliations
- University of Aberdeen (GB)
- University of Manchester (GB)
- The Queen's Medical Research Institute (GB)
- Corresponding author
- Dardente, Hugues
- Hazlerigg, David G.
- ORCID
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2010-12
- Volume
- 20
- Issue
- 24
- Pages
- 2193-2198
- ISSN
- 0960-9822 (ISSN-L)
- OpenAlex
- W2062566674
- Cited by
- 291
- References
- 35
- Citations by year
- 2026: 9 · 2025: 16 · 2024: 17 · 2023: 23 · 2022: 17 · 2021: 32 · 2020: 21 · 2019: 9 · 2018: 19 · 2017: 23 · 2016: 6 · 2015: 18 · 2014: 25 · 2013: 21 · 2012: 18
- FWCI
- 8.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Current Biology (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- HAL (submittedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Funders
- Biotechnology and Biological Sciences Research Council (BB/G003033/1)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- photoperiod, circadian clock, pars tuberalis, melatonin, seasonal timing, Soay sheep
- MeSH terms
- Animals, Base Sequence, DNA-Binding Proteins, Humans, Mammals, Melatonin, Molecular Sequence Data, Pituitary Gland, Promoter Regions, Genetic, Seasons, Sheep, Transcription, Genetic, Sequence Alignment, Protein Tyrosine Phosphatases, Photoperiod, Thyrotropin, beta Subunit, Basic-Leucine Zipper Transcription Factors, Circadian Clocks
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