ArticleJournal of molecular medicine (Berlin, Germany)2012
An intronic MYLK variant associated with inflammatory lung disease regulates promoter activity of the smooth muscle myosin light chain kinase isoform.
Article in Journal of molecular medicine (Berlin, Germany), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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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
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Effect of metabolic genetic variants on long-term disease comorbidity in patients with type 2 diabetes.Scientific reports · 2021Pooled it
- Hypothalamic Norepinephrine Concentration and Heart Mass in Hypertensive ISIAH Rats Are Associated with a Genetic Locus on Chromosome 18.Journal of personalized medicine · 2021Article
- Hypoxic modulation of fetal vascular MLCK abundance, localization, and function.American journal of physiology. Regulatory, integrative and comparative physiology · 2021Article
- Single-Nucleotide Polymorphisms (SNPs) Both Associated with Hypertension and Contributing to Accelerated-Senescence Traits in OXYS Rats.International journal of molecular sciences · 2020Article
- Single nucleotide polymorphisms in the MYLKP1 pseudogene are associated with increased colon cancer risk in African Americans.PloS one · 2018Article
- Epigenetic contribution of the myosin light chain kinase gene to the risk for acute respiratory distress syndrome.Translational research : the journal of laboratory and clinical medicine · 2017Article
- Mechanical Stress and Single Nucleotide Variants Regulate Alternative Splicing of the MYLK Gene.American journal of respiratory cell and molecular biology · 2017Article
- Functionality and opposite roles of two interleukin 4 haplotypes in immune cells.Genes and immunity · 2017Article
- The structural origin of metabolic quantitative diversity.Scientific reports · 2016Article
- ROCK2 and MYLK variants under hypobaric hypoxic environment of high altitude associate with high altitude pulmonary edema and adaptation.The application of clinical genetics · 2015Article
- Nonmuscle myosin light chain kinase regulates murine asthmatic inflammation.American journal of respiratory cell and molecular biology · 2014Article
- GADD45a promoter regulation by a functional genetic variant associated with acute lung injury.PloS one · 2014Article
- Regulation of 130-kDa smooth muscle myosin light chain kinase expression by an intronic CArG element.The Journal of biological chemistry · 2013Article
- Functional promoter variants in sphingosine 1-phosphate receptor 3 associate with susceptibility to sepsis-associated acute respiratory distress syndrome.American journal of physiology. Lung cellular and molecular physiology · 2013Article
- Review
- Lack of correlation between in silico projection of function and quantitative real-time PCR-determined gene expression levels in colon tissue.Pharmacogenomics and personalized medicine · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Intronic single-nucleotide polymorphisms (SNPs) are commonly associated with complex diseases but exhibit unknown biologic functionality. Myosin light-chain kinase (MLCK), a central cytoskeletal regulator encoded by MYLK, plays a key pathophysiological role in complex diseases including acute lung injury (ALI) and asthma. We studied the potential regulatory roles of two intronic MYLK SNPs (rs936170 and rs820336) previously associated with ALI and asthma. Due to their genomic location at the junction encoding the non-muscle and smooth muscle MLCK (smMLCK) isoforms, we first identified the transcription start site (TSS) of the smMLCK isoform, and isolated a 2,954-bp DNA fragment upstream of the smMLCK TSS. Serial 5' deletion of the fragment revealed a proximal promoter region exhibiting strong promoter activity with potential inhibitory elements in the distal region. Site-directed mutageneses and luciferase reporter assays showed no effect of the distal promoter SNP rs936170 on smMLCK promoter activity. In contrast, SNP rs820336, located in an enhancer/repressor region downstream of TSS, was identified to regulate smMLCK promoter activity in an allelic-dependent manner. The A allele interrupted the binding site for Forkhead box protein N1 (FOXN1), a transcription factor governing expression of immune response genes. Silencing of FOXN1 expression (siRNA) reduced FOXN1 interaction with cis-regulatory elements in proximity to rs820336 and significantly decreased smMLCK expression. These functional insights into the involvement of intronic MYLK SNPs further strengthen the concept that MYLK contributes to inflammatory disease susceptibility and represents an attractive molecular target in complex inflammatory disorders.
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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.