Evidence map›Paper›PMID 30954403›Full record

ArticleMolecular cell2019

The Phospho-Code Determining Circadian Feedback Loop Closure and Output in Neurospora.

Bin Wang, Arminja N Kettenbach, Xiaoying Zhou, Jennifer J Loros, Jay C Dunlap

Open access · bronzeAbstract read
In one paragraph

Article in Molecular cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
4.6field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

45 citing papers in PubMed, 84 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. A daily cycle of White Collar Complex dephosphorylation sustains circadian rhythmicity inProceedings of the National Academy of Sciences of the United States of America · 2026
    Article
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  6. Article
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  8. Review
  9. Alternative splicing ofProceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  10. Phosphorylation of DNA-binding domains of CLOCK-BMAL1 complex for PER-dependent inhibition in circadian clock of mammalian cells.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  11. Alternative splicing ofbioRxiv : the preprint server for biology · 2024
    Article
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  16. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Bin WangDepartment of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA.
Arminja N KettenbachNorris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA; Department of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA.
Xiaoying ZhouDepartment of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA.
Jennifer J LorosDepartment of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA; Department of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA.
Jay C DunlapDepartment of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA. Electronic address: jay.c.dunlap@dartmouth.edu.
Dartmouth College · US

Funding

Genetic and Molecular Dissection of the Neurospora ClockR35GM118021 · NIGMS · DARTMOUTH COLLEGE · PI Jay C. Dunlap · 2016 to 2026
$7.3M
Phosphorylation Signaling by Phosphoprotein PhosphatasesR35GM119455 · NIGMS · DARTMOUTH COLLEGE · PI Arminja Nadine Kettenbach · 2016 to 2026
$5.1M
Identification and Analysis of Circadian Clock-Controlled GenesR35GM118022 · NIGMS · DARTMOUTH COLLEGE · PI LOROS, JENNIFER J. · 2016 to 2021
$3.7M
LC-Orbitrap MS/MS System for shotgun Proteomics at DartmouthS10OD016212 · OD · DARTMOUTH COLLEGE · PI GERBER, SCOTT A. · 2013 to 2013
$600k
NIGMS NIH HHS R35 GM118021NIGMS NIH HHS R35 GM118022NIGMS NIH HHS R35 GM119455NIH HHS S10 OD016212
6 · The paper itself

Abstract

In the negative feedback loop driving fungal and animal circadian oscillators, negative elements (FREQUENCY [FRQ], PERIODS [PERs], and CRYPTOCHROMES [CRYs]) are understood to inhibit their own expression, in part by promoting the phosphorylation of their heterodimeric transcriptional activators (e.g., White Collar-1 [WC-1]-WC-2 [White Collar complex; WCC] and BMAL1/Circadian Locomotor Output Cycles Kaput [CLOCK]). However, correlations between heterodimer activity and phosphorylation are weak, contradictions exist, and mechanistic details are almost wholly lacking. We report mapping of 80 phosphosites on WC-1 and 15 on WC-2 and elucidation of the time-of-day-specific code, requiring both a group of phosphoevents on WC-1 and two distinct clusters on WC-2, that governs circadian repression, leading to feedback loop closure. Combinatorial control via phosphorylation also governs rhythmic WCC binding to the promoters of clock-controlled genes mediating the essential first step in circadian output, a group encoding both transcription factors and signaling proteins. These data provide a basic mechanistic understanding for fundamental events underlying circadian negative feedback and output, key aspects of circadian biology.

Indexed as

ARNTL Transcription FactorsCircadian RhythmDNA-Binding ProteinsFeedback, PhysiologicalFungal ProteinsGene Expression Regulation, FungalNeurospora crassaPhosphorylationPromoter Regions, GeneticSignal TransductionTranscription FactorsARNTL Transcription FactorsDNA-Binding ProteinsFungal ProteinsTranscription Factorswc-1 protein, Neurospora crassawhite collar 2 protein, NeurosporaC-boxccgsclock-controlled genesDNA bindingfeedback loopFRQfrq transcriptionphosphorylationWC-1WC-2

Identifiers

PMID30954403
PMCPMC6583785
OpenAlexW2934823619

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.