Evidence map›Paper›PMID 21797989›Full record

ArticleSkeletal muscle2011

Differentiation and fiber type-specific activity of a muscle creatine kinase intronic enhancer.

Phillip Wl Tai, Katherine I Fisher-Aylor, Charis L Himeda, Catherine L Smith, Alexandra P Mackenzie, Deri L Helterline, John C Angello, Robert E Welikson, Barbara J Wold, Stephen D Hauschka

Open access · goldAbstract read
In one paragraph

Article in Skeletal muscle, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
0.9field-weighted citation impact, top 27% 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

23 citing papers in PubMed, 34 citations in OpenAlex.

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  10. Creatine Kinase and Myoglobin Plasma Levels in Mountain Bike and Road Cyclists 1 h after the Race.International journal of environmental research and public health · 2022
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  13. A Muscle Hybrid Promoter as a Novel Tool for Gene Therapy.Molecular therapy. Methods & clinical development · 2019
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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

10 authors at 3 institutions in 1 country.

Phillip Wl TaiDepartment of Biochemistry, 1705 NE Pacific St,, University of Washington, Seattle, WA 98195, USA. haus@u.washington.edu.
Katherine I Fisher-Aylor
Charis L Himeda
Catherine L Smith
Alexandra P Mackenzie
Deri L Helterline
John C Angello
Robert E Welikson
Barbara J Wold
Stephen D Hauschka
Seattle University · USUniversity of Washington · USCalifornia Institute of Technology · US

Funding

INTERDISCIPLINARY TRAINING IN DEVELOPMENTAL BIOLOGYT32HD007183 · NICHD · UNIVERSITY OF WASHINGTON · PI RAIBLE, DAVID W · 1985 to 2015
$5.7M
Striated Muscle Gene Transcription and Regulatory Gene Cassettes for Gene TherapyR01AR018860 · NIAMS · UNIVERSITY OF WASHINGTON · PI HAUSCHKA, STEPHEN DENISON · 1986 to 2012
$3.4M
NIAMS NIH HHS R01 AR018860NICHD NIH HHS T32 HD007183
6 · The paper itself

Abstract

backgroundHundreds of genes, including muscle creatine kinase (MCK), are differentially expressed in fast- and slow-twitch muscle fibers, but the fiber type-specific regulatory mechanisms are not well understood.

resultsModulatory region 1 (MR1) is a 1-kb regulatory region within MCK intron 1 that is highly active in terminally differentiating skeletal myocytes in vitro. A MCK small intronic enhancer (MCK-SIE) containing a paired E-box/myocyte enhancer factor 2 (MEF2) regulatory motif resides within MR1. The SIE's transcriptional activity equals that of the extensively characterized 206-bp MCK 5'-enhancer, but the MCK-SIE is flanked by regions that can repress its activity via the individual and combined effects of about 15 different but highly conserved 9- to 24-bp sequences. ChIP and ChIP-Seq analyses indicate that the SIE and the MCK 5'-enhancer are occupied by MyoD, myogenin and MEF2. Many other E-boxes located within or immediately adjacent to intron 1 are not occupied by MyoD or myogenin. Transgenic analysis of a 6.5-kb MCK genomic fragment containing the 5'-enhancer and proximal promoter plus the 3.2-kb intron 1, with and without MR1, indicates that MR1 is critical for MCK expression in slow- and intermediate-twitch muscle fibers (types I and IIa, respectively), but is not required for expression in fast-twitch muscle fibers (types IIb and IId).

conclusionsIn this study, we discovered that MR1 is critical for MCK expression in slow- and intermediate-twitch muscle fibers and that MR1's positive transcriptional activity depends on a paired E-box MEF2 site motif within a SIE. This is the first study to delineate the DNA controls for MCK expression in different skeletal muscle fiber types.

Identifiers

PMID21797989
PMCPMC3157005
OpenAlexW1991625931

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.