Prep1/Pbx2 complexes regulate CCL2 expression through the −2578 guanine polymorphism

Wright, Edward K.; Page, Stephen H.; Barber, Sheila A.; Clements, Janice E.

doi:10.1038/gene.2008.33

Cited by 24 publications

(31 citation statements)

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“…However, a promoter assay in vitro does not necessarily represent the gene expression in vivo . Second, regulation of promoter activity by the length of (GT)n repeats may differ in cell types in response to stimuli [18, 19], and the influence of a specific allele on the promoter activity may change during inflammatory conditions [32]. Third, many HMOX1 association studies were conducted in Japanese and Chinese populations.…”

Section: Discussionmentioning

confidence: 99%

Heme Oxygenase-1 microsatellite polymorphism and haplotypes are associated with the development of acute respiratory distress syndrome

et al. 2009

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Objective-Heme oxygenase-1 (HO-1) acts in cytoprotection against acute lung injury. The polymorphic (GT)n repeat in the HO-1 gene (HMOX1) promoter regulates HMOX1 expression. We investigated the associations of HMOX1 polymorphisms with ARDS risk and plasma HO-1 levels.Design-Unmatched, nested case-control study. Setting-Academic medical center.Patients-Consecutive patients with ARDS risk factors upon ICU admission were prospectively enrolled. Cases were 437 Caucasians who developed ARDS and controls were 1014 Caucasians who did not.Measurements and results-We genotyped the (GT)n polymorphism and three tagging single nucleotide polymorphisms (tSNPs) in 1451 patients, and measured the plasma HO-1 levels in 106 ARDS patients. We clustered the (GT)n repeats into: S-allele (< 24 repeats), M-allele (24-30 repeats) and L-allele (≥ 31 repeats). We found that longer (GT)n repeats were associated with reduced ARDS risk (P trend = 0.004 for both alleles and genotypes), but no individual tSNP was associated with ARDS risk. HMOX1 haplotypes were significantly associated with ARDS risk (global test, P = 0.016), and the haplotype S-TAG was associated with increased ARDS risk (OR, 1.75; 95% CI, 1.15-2.68; P = 0.010). Intermediate-phenotype analysis showed longer (GT)n repeats were associated with higher plasma HO-1 levels (P trend = 0.019 for alleles and 0.027 for genotypes).Conclusions-Longer (GT)n repeats in the HMOX1 promoter are associated with higher plasma HO-1 levels and reduced ARDS risk. The common haplotype S-TAG is associated with increased ARDS risk. Our results suggest that HMOX1 variation may modulate ARDS risk through the promoter microsatellite polymorphism.

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Section: Discussionmentioning

confidence: 99%

Heme Oxygenase-1 microsatellite polymorphism and haplotypes are associated with the development of acute respiratory distress syndrome

et al. 2009

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“…32 P]ATP-labeled oligonucleotides as described previously (30). Incubation was carried out in binding reaction buffer containing 1 mM MgCl 2 , 60 mM KCl, 0.1 mM EDTA, 20 mM HEPES (pH 8.0), 15% glycerol, and 1 g of poly(dI-dC) as nonspecific competitor.…”

Section: Methodsmentioning

confidence: 99%

Regulation of SIVmac239 Basal Long Terminal Repeat Activity and Viral Replication in Macrophages

Ravimohan

Gama

Barber

et al. 2010

Journal of Biological Chemistry

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CCAAT/enhancer-binding protein (C/EBP) ␤ and C/EBP sites in the HIV-1 long terminal repeat (LTR) are crucial for HIV-1 replication in monocyte/macrophages and for the ability of interferon ␤ (IFN␤) to inhibit ongoing active HIV replication in these cells. This IFN␤-mediated down-regulation involves induction of the truncated, dominant-negative isoform of C/EBP␤ referred to as liver-enriched transcriptional inhibitory protein (LIP). Although binding of the C/EBP␤ isoform to C/EBP sites in the simian immunodeficiency virus (SIV) LTR has previously been examined, the importance of these sites in core promoter-mediated transcription, virus replication, IFN␤-mediated regulation, and the relative binding of the two isoforms (C/EBP␤ and LIP) has not been investigated. Here, we specifically examine two C/EBP sites, JC1 (؊100 bp) and DS1 (؉134 bp), located within the minimal region of the SIV LTR, required for core promoter-mediated transcription and virus replication in macrophages. Our studies revealed that the JC1 but not DS1 C/EBP site is important for basal level transcription, whereas the DS1 C/EBP site is imperative for productive virus replication in primary macrophages. In contrast, either JC1 or DS1 C/EBP site is sufficient to mediate IFN␤-induced down-regulation of SIV LTR activity and virus replication in these cells. We also characterized the differential binding properties of C/EBP␤ and LIP to the JC1 and DS1 sites. In conjunction with previous studies from our laboratory, we demonstrate the importance of these sites in virus gene expression, and we propose a model for their role in establishing latency and persistence in macrophages in the brain.

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“…23 Indeed, one study by Wright and colleagues demonstrated that Prep1/Pbx2 nuclear complexes could bind the −2578G oligonucleotides (TGACAG) in the CCL2 promoter region and repress the expression of this gene compared to the A allele. 19 However, upon interleukin-1β (IL-1β) stimulation, the transcription levels from promoters that harbored the A or G allele were equally activated, despite the Prep1/Pbx2 complexes binding the −2578 G allele; suggesting that the repressive effect of the Prep1/Pbx2 complexes may be overcome by the other potent or dominant transcriptional activators such as nuclear factor like (NF)-κB during IL-1β stimulation. Indeed, there is some evidence that both CCL2 gene and NF-κB are involved in the pathogenic mechanism of the AR.…”

Section: Discussionmentioning

confidence: 99%

“…Previous study on the whole-mount in situ hybridization investigation of murine gestation found that the Pbx2 gene expressed throughout the mouse embryo, and a high level of expression of Pbx2 was observed in the epidermal layer of the developing skin and the vibrissae. 19 Furthermore, at embryonic day 15.5 (E15.5), the expression of Pbx2 was particularly prominent in epithelial structures, including those lining the nasal cavity, cochlear ducts, and tubotympanic recess, as well as the respiratory epithelium lining the segmental bronchi of the lung. 20 The finding for the expression of Pbx2 in the epithelial layer lining the upper airway of murine gestation suggests that this gene may be involved in development of mechanisms underlying the pathology of AR and asthma.…”

Section: Discussionmentioning

confidence: 99%

Variant of PBX2 gene in the 6p21.3 asthma susceptibility locus is associated with allergic rhinitis in Chinese subjects

Zhao

Zhang

2016

Int Forum Allergy Rhinol

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Prep1/Pbx2 complexes regulate CCL2 expression through the −2578 guanine polymorphism

Cited by 24 publications

References 50 publications

Heme Oxygenase-1 microsatellite polymorphism and haplotypes are associated with the development of acute respiratory distress syndrome

Heme Oxygenase-1 microsatellite polymorphism and haplotypes are associated with the development of acute respiratory distress syndrome

Regulation of SIVmac239 Basal Long Terminal Repeat Activity and Viral Replication in Macrophages

Variant of PBX2 gene in the 6p21.3 asthma susceptibility locus is associated with allergic rhinitis in Chinese subjects

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