Evidence map›Paper›PMID 14966291›Full record

ArticleMolecular and cellular biology2004

Quantitative proteomic identification of six4 as the trex-binding factor in the muscle creatine kinase enhancer.

Charis L Himeda, Jeffrey A Ranish, John C Angello, Pascal Maire, Ruedi Aebersold, Stephen D Hauschka

Open access · greenAbstract read
In one paragraph

Article in Molecular and cellular biology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

31 citing papers in PubMed, 77 citations in OpenAlex.

  1. Ets2 Is an Activity-Dependent Transcriptional Regulator of a Fast-Twitch Muscle Program.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
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  7. Transcriptional regulation of cranial sensory placode development.Current topics in developmental biology · 2015
    Review
  8. Chromatin enrichment for proteomics.Nature protocols · 2014
    Article
  9. Article
  10. The EYA-SO/SIX complex in development and disease.Pediatric nephrology (Berlin, Germany) · 2013
    Review
  11. The Eyes Absent proteins in development and disease.Cellular and molecular life sciences : CMLS · 2013
    Review
  12. Article
  13. Review
  14. Article
  15. Article
  16. Review
  17. Article
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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

6 authors at 3 institutions in 2 countries.

Charis L HimedaDepartment of Biochemistry, University of Washington, Seattle, Washington 98195, USA.
Jeffrey A Ranish
John C Angello
Pascal Maire
Ruedi Aebersold
Stephen D Hauschka
University of Washington · USInstitute for Systems Biology · USInstitut Cochin · FR

Funding

TRAINING IN MOLECULAR AND CELLULAR BIOLOGYT32GM007270 · NIGMS · UNIVERSITY OF WASHINGTON · PI RAIBLE, DAVID W · 1985 to 2020
$21.0M
Striated Muscle Gene Transcription and Regulatory Gene Cassettes for Gene TherapyR01AR018860 · NIAMS · UNIVERSITY OF WASHINGTON · PI HAUSCHKA, STEPHEN DENISON · 1986 to 2012
$3.4M
REGULATION OF SKELETAL MUSCLE DIFFERENTIATIONR37AR018860 · NIAMS · UNIVERSITY OF WASHINGTON · PI HAUSCHKA, STEPHEN DENISON · 1993 to 2002
$1.0M
NHLBI PROTEOMICS INITIATIVE-268028179N01HV028179 · HV · INSTITUTE FOR SYSTEMS BIOLOGY · 2002 to 2002
–
NHLBI NIH HHS N01 HV028179NHLBI NIH HHS N01-HV-28179NIAMS NIH HHS AR18860NIAMS NIH HHS R01 AR018860NIAMS NIH HHS R37 AR018860NIGMS NIH HHS GM07270NIGMS NIH HHS T32 GM007270PHS HHS R24 64387
6 · The paper itself

Abstract

Transcriptional regulatory element X (Trex) is a positive control site within the Muscle creatine kinase (MCK) enhancer. Cell culture and transgenic studies indicate that the Trex site is important for MCK expression in skeletal and cardiac muscle. After selectively enriching for the Trex-binding factor (TrexBF) using magnetic beads coupled to oligonucleotides containing either wild-type or mutant Trex sites, quantitative proteomics was used to identify TrexBF as Six4, a homeodomain transcription factor of the Six/sine oculis family, from a background of approximately 900 copurifying proteins. Using gel shift assays and Six-specific antisera, we demonstrated that Six4 is TrexBF in mouse skeletal myocytes and embryonic day 10 chick skeletal and cardiac muscle, while Six5 is the major TrexBF in adult mouse heart. In cotransfection studies, Six4 transactivates the MCK enhancer as well as muscle-specific regulatory regions of Aldolase A and Cardiac troponin C via Trex/MEF3 sites. Our results are consistent with Six4 being a key regulator of muscle gene expression in adult skeletal muscle and in developing striated muscle. The Trex/MEF3 composite sequence ([C/A]ACC[C/T]GA) allowed us to identify novel putative Six-binding sites in six other muscle genes. Our proteomics strategy will be useful for identifying transcription factors from complex mixtures using only defined DNA fragments for purification.

Indexed as

Enhancer Elements, GeneticGene Expression Regulation, EnzymologicGenes, RegulatorTrans-ActivatorsAnimalsCells, CulturedChick EmbryoCreatine KinaseCreatine Kinase, MM FormDNA-Binding ProteinsHeLa CellsHomeodomain ProteinsHumansImmunomagnetic SeparationIsoenzymesMiceCreatine KinaseCreatine Kinase, MM FormDNA-Binding ProteinsHomeodomain ProteinsIsoenzymesMEF-3 protein, humanNerve Tissue ProteinsNuclear ProteinsSIX4 protein, humanSix4 protein, mouseSIX5 protein, humanSix5 protein, mouseTrans-ActivatorsTranscription Factors

Identifiers

PMID14966291
PMCPMC350548
OpenAlexW2150315530

What OpenQuestion holds

Textmetadata
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.