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April 1, 1999Journal of Biological ChemistryOpen Access

The Role of GATA, CArG, E-box, and a Novel Element in the Regulation of Cardiac Expression of the Na+-Ca2+ Exchanger Gene

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Key result

SRF and GATA-4 binding to elements at -80 and -50 are critical for NCX1 expression, while the -172 E-box and a novel enhancer (+103 to +134) are required for phenylephrine up-regulation.

Population

Neonatal cardiomyocytes

Design

Preclinical

Authors

GCGuangmao ChengBrown UniversityTHTyson P. HagenColorado Permanente Medical GroupMDMyra L. DawsonMedical University of South Carolina

Discussion

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Implication

These mechanisms remain preclinical; leaves open targeted NCX1 promoter studies in human hypertrophy models.

Structured PICO

P
Population
Neonatal cardiomyocytes
I
Intervention
Alpha-adrenergic stimulation with phenylephrine and promoter mutational/deletion analysis
O
Outcome
NCX1 gene expression and alpha-adrenergic up-regulationsurrogate

Identification of specific promoter elements (CArG, GATA, E-box) and transcription factors (SRF, GATA-4) provides insight into the molecular mechanisms of NCX1 up-regulation during cardiac hypertrophy.

Cite This Study

Cheng et al. (1999) studied this question. SRF and GATA-4 binding to elements at -80 and -50 are critical for NCX1 expression, while the -172 E-box and a novel enhancer (+103 to +134) are required for phenylephrine up-regulation.

synapsesocial.com/papers/6a0d51f2cae7912d2fa4e72ehttps://doi.org/10.1074/jbc.274.18.12819
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Cloning of Cardiac, Kidney, and Brain Promoters of the Feline ncx1 Gene1997 · 65 citations
  2. 2GATA-4 and Nkx-2.5 Coactivate Nkx-2 DNA Binding Targets: Role for Regulating Early Cardiac Gene Expression1998 · 304 citations
  3. 3Activation of the cardiac α-actin promoter depends upon serum response factor,Tinman homologue, Nkx-2.5, and intact serum response elements1996 · 121 citations
  4. 4Phosphorylation-dependent Regulation of Cardiac Na+/Ca2+ Exchanger via Protein Kinase C1996 · 189 citations
  5. 5Multiple regulatory elements contribute differentially to muscle creatine kinase enhancer activity in skeletal and cardiac muscle.1993 · 140 citations