Evidence map›Paper›PMID 18177499›Full record

ArticleBMC molecular biology2008

A direct repeat of E-box-like elements is required for cell-autonomous circadian rhythm of clock genes.

Yasukazu Nakahata, Mayumi Yoshida, Atsuko Takano, Haruhiko Soma, Takuro Yamamoto, Akio Yasuda, Toru Nakatsu, Toru Takumi

Registry-linked trialOpen access · hybridAbstract read
In one paragraph

Article in BMC molecular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04637399 (Circadian Misalignment as a Disease Risk Factor in Inflammatory Bowel Disease), which is not on this map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
3.5field-weighted citation impact, top 6% 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.

NCT04637399 completednot on this mapstarted 2016, after this paper: background citation

Circadian Misalignment as a Disease Risk Factor in Inflammatory Bowel Disease

TypeobservationalSponsorRush University Medical CenterRan2016 to 2021Enrolled52ConditionsInflammatory Bowel Diseases, Crohn Disease, Ulcerative Colitis
3 · Its place in the literature

Who cites it

48 citing papers in PubMed, 204 citations in OpenAlex.

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  3. AProceedings of the National Academy of Sciences of the United States of America · 2026
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  16. Mechanisms of Binding Specificity among bHLH Transcription Factors.International journal of molecular sciences · 2021
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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

8 authors at 3 institutions in 2 countries.

Yasukazu NakahataOsaka Bioscience Institute, Suita, Osaka 565-0874, Japan. yasu_nakahata@yahoo.co.jp
Mayumi Yoshida
Atsuko Takano
Haruhiko Soma
Takuro Yamamoto
Akio Yasuda
Toru Nakatsu
Toru Takumi
Kyoto University · JPSony (Taiwan) · TWSony Computer Science Laboratories · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe circadian expression of the mammalian clock genes is based on transcriptional feedback loops. Two basic helix-loop-helix (bHLH) PAS (for Period-Arnt-Sim) domain-containing transcriptional activators, CLOCK and BMAL1, are known to regulate gene expression by interacting with a promoter element termed the E-box (CACGTG). The non-canonical E-boxes or E-box-like sequences have also been reported to be necessary for circadian oscillation.

resultsWe report a new cis-element required for cell-autonomous circadian transcription of clock genes. This new element consists of a canonical E-box or a non-canonical E-box and an E-box-like sequence in tandem with the latter with a short interval, 6 base pairs, between them. We demonstrate that both E-box or E-box-like sequences are needed to generate cell-autonomous oscillation. We also verify that the spacing nucleotides with constant length between these 2 E-elements are crucial for robust oscillation. Furthermore, by in silico analysis we conclude that several clock and clock-controlled genes possess a direct repeat of the E-box-like elements in their promoter region.

conclusionWe propose a novel possible mechanism regulated by double E-box-like elements, not to a single E-box, for circadian transcriptional oscillation. The direct repeat of the E-box-like elements identified in this study is the minimal required element for the generation of cell-autonomous transcriptional oscillation of clock and clock-controlled genes.

Indexed as

E-Box ElementsAnimalsARNTL Transcription FactorsBase SequenceBasic Helix-Loop-Helix ProteinsCircadian RhythmCLOCK ProteinsDNAHumansMacromolecular SubstancesMiceModels, GeneticModels, MolecularMutationNIH 3T3 CellsNuclear ProteinsARNTL Transcription FactorsBasic Helix-Loop-Helix ProteinsBMAL1 protein, humanBmal1 protein, mouseCLOCK protein, humanClock protein, mouseCLOCK ProteinsDNAMacromolecular SubstancesNuclear ProteinsPER2 protein, humanPeriod Circadian ProteinsTrans-ActivatorsTranscription Factors

Identifiers

PMID18177499
PMCPMC2254435
OpenAlexW2006623829

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Registered trials

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.