ArticleProceedings of the National Academy of Sciences of the United States of America2012
Evolution of CpG island promoter function underlies changes in KChIP2 potassium channel subunit gene expression in mammalian heart.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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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.
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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.
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Who cites it
3 citing papers in PubMed, 7 citations in OpenAlex.
- Transmural gradients in ion channel and auxiliary subunit expression.Progress in biophysics and molecular biology · 2016Review
- Regulatory evolution and voltage-gated ion channel expression in squid axon: selection-mutation balance and fitness cliffs.PloS one · 2015Article
- Comparative analysis using K-mer and K-flank patterns provides evidence for CpG island sequence evolution in mammalian genomes.Nucleic acids research · 2013Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
Abstract
Scaling of cardiac electrophysiology with body mass requires large changes in the ventricular action potential duration and heart rate in mammals. These changes in cellular electrophysiological function are produced by systematic and coordinated changes in the expression of multiple ion channel and transporter genes. Expression of one important potassium current, the transient outward current (I(to)), changes significantly during mammalian evolution. Changes in I(to) expression are determined, in part, by variation in the expression of an obligatory auxiliary subunit encoded by the KChIP2 gene. The KChIP2 gene is expressed in both cardiac myocytes and neurons and transcription in both cell types is initiated from the same CpG island promoter. Species-dependent variation of KChIP2 expression in heart is mediated by the evolution of the cis-regulatory function of this gene. Surprisingly, the major locus of evolutionary change for KChIP2 gene expression in heart lies within the CpG island core promoter. The results demonstrate that CpG island promoters are not simply permissive for gene expression but can also contribute to tissue-selective expression and, as such, can function as an important locus for the evolution of cis-regulatory function. More generally, evolution of the cis-regulatory function of voltage-gated ion channel genes appears to be an effective and efficient way to modify channel expression levels to optimize electrophysiological function.
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Registered trials
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