Transcriptional rewiring of an evolutionarily conserved circadian clock

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dc.contributor.authorGoity, Alejandra
dc.contributor.authorDovzhenok, Andrey
dc.contributor.authorLim, Sookkyung
dc.contributor.authorHong, Christian
dc.contributor.authorLoros, Jennifer
dc.contributor.authorDunlap, Jay C.
dc.contributor.authorLarrondo, Luis F.
dc.date.accessioned2025-01-20T16:18:05Z
dc.date.available2025-01-20T16:18:05Z
dc.date.issued2024
dc.description.abstractCircadian clocks temporally coordinate daily organismal biology over the 24-h cycle. Their molecular design, preserved between fungi and animals, is based on a core-oscillator composed of a one-step transcriptional-translational-negative-feedback-loop (TTFL). To test whether this evolutionarily conserved TTFL architecture is the only plausible way for achieving a functional circadian clock, we adopted a transcriptional rewiring approach, artificially co-opting regulators of the circadian output pathways into the core-oscillator. Herein we describe one of these semi-synthetic clocks which maintains all basic circadian features but, notably, it also exhibits new attributes such as a "lights-on timer" logic, where clock phase is fixed at the end of the night. Our findings indicate that fundamental circadian properties such as period, phase and temperature compensation are differentially regulated by transcriptional and posttranslational aspects of the clockworks.
dc.description.abstractEukaryotic circadian oscillators share a one-step transcription-translation negative-feedback loop (TTFL) circuit design, where a main transcriptional complex drives expression of a negative element that can inhibit its own expression. Here, a transcriptional rewiring strategy in the fungus N. crassa reveals that this basic circuit topology can be dramatically changed, while still yielding a functional semi-synthetic clock.Placing the transcription of the negative component frq under the control of the output promoter con-10 alters its regulation, while still yielding rhythmic expression. In the resulting functional semi-synthetic circuit, frq expression is now under the control of circadian clock downstream components. FRQ phosphorylation has a more pronounced effect on circadian period length and temperature compensation than its transcriptional regulation. In the semi-synthetic oscillator, the circadian rhythm phase is now determined by the moment the light is turned on.
dc.description.abstractCo-option of downstream transcription factors into the main transcriptional circuit of the circadian clock in the fungus Neurospora crassa leads to altered clock phase determination.
dc.fuente.origenWOS
dc.identifier.doi10.1038/s44318-024-00088-3
dc.identifier.eissn1460-2075
dc.identifier.issn0261-4189
dc.identifier.urihttps://doi.org/10.1038/s44318-024-00088-3
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/90630
dc.identifier.wosidWOS:001227339800001
dc.issue.numero10
dc.language.isoen
dc.pagina.final2034
dc.pagina.inicio2015
dc.revistaEmbo journal
dc.rightsacceso restringido
dc.subjectCircadian Rhythms
dc.subjectTranscriptional Rewiring
dc.subjectNeurospora
dc.subjectSynthetic Biology
dc.subjectPhotoresponses
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleTranscriptional rewiring of an evolutionarily conserved circadian clock
dc.typeartículo
dc.volumen43
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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