A balance between activating and repressive histone modifications regulates<i>cystic fibrosis transmembrane conductance regulator (CFTR</i>) expression in vivo

Bergougnoux, Anne; Rivals, Isabelle; Liquori, Alessandro; Raynal, Caroline; Varilh, Jessica; Magalhães, Milena; Perez, Marie-José; Bigi, Nicole; Georges, Marie des; Chiron, R.; Squalli-Houssaini, Ahmed Saad; Claustres, Mireille; Sario, Albertina De

doi:10.4161/epi.28967

Cited by 15 publications

(10 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…NEC collected in RNAprotect Cell Reagent (#76526 QIAGEN) were treated with 1 mg/mL RNAse. Genomic DNA was extracted using the QIAamp DNA Micro Kit (#56304, QIAGEN) as previously described [ 39 ]. The mean DNA yield was 5.1 ± 2.8 μg in controls and 3.9 ± 3.1 μg in CF patients (range 0 to 12.4 μg).…”

Section: Methodsmentioning

confidence: 99%

DNA methylation at modifier genes of lung disease severity is altered in cystic fibrosis

et al. 2017

Self Cite

View full text Add to dashboard Cite

BackgroundLung disease progression is variable among cystic fibrosis (CF) patients and depends on DNA mutations in the CFTR gene, polymorphic variations in disease modifier genes, and environmental exposure. The contribution of genetic factors has been extensively investigated, whereas the mechanism whereby environmental factors modulate the lung disease is unknown. In this project, we hypothesized that (i) reiterative stress alters the epigenome in CF-affected tissues and (ii) DNA methylation variations at disease modifier genes modulate the lung function in CF patients.ResultsWe profiled DNA methylation at CFTR, the disease-causing gene, and at 13 lung modifier genes in nasal epithelial cells and whole blood samples from 48 CF patients and 24 healthy controls. CF patients homozygous for the p.Phe508del mutation and ≥18-year-old were stratified according to the lung disease severity. DNA methylation was measured by bisulfite and next-generation sequencing. The DNA methylation profile allowed us to correctly classify 75% of the subjects, thus providing a CF-specific molecular signature. Moreover, in CF patients, DNA methylation at specific genes was highly correlated in the same tissue sample. We suggest that gene methylation in CF cells may be co-regulated by disease-specific trans-factors. Three genes were differentially methylated in CF patients compared with controls and/or in groups of pulmonary severity: HMOX1 and GSTM3 in nasal epithelial samples; HMOX1 and EDNRA in blood samples. The association between pulmonary severity and DNA methylation at EDNRA was confirmed in blood samples from an independent set of CF patients. Also, lower DNA methylation levels at GSTM3 were associated with the GSTM3*B allele, a polymorphic 3-bp deletion that has a protective effect in cystic fibrosis.ConclusionsDNA methylation levels are altered in nasal epithelial and blood cell samples from CF patients. Analysis of CFTR and 13 lung disease modifier genes shows DNA methylation changes of small magnitude: some of them are a consequence of the disease; other changes may result in small expression variations that collectively modulate the lung disease severity.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-016-0300-8) contains supplementary material, which is available to authorized users.

show abstract

Section: Methodsmentioning

confidence: 99%

DNA methylation at modifier genes of lung disease severity is altered in cystic fibrosis

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…NECs are collected from the inferior turbinate using sterile brushes [20,[27][28][29][30] or plastic curettes (Rhino-probe, Arlington Scientific, TX, USA) [31][32][33][34][35] (Figure 2). To remove mucus, volunteers are generally asked to blow their nose.…”

Section: Nec Collection Is Minimally Invasivementioning

confidence: 99%

“…Finally, in a study aiming to determine whether epigenetic mechanisms regulate CFTR tissue-restricted expression, we analyzed DNA methylation in NEC collected from healthy volunteers by two approaches: locusspecific pyrosequencing and targeted next-generation sequencing [35].…”

Section: Dna Methylation Analysis In Necmentioning

confidence: 99%

Nasal Epithelial Cells: A Tool to Study Dna Methylation in Airway Diseases

2015

Self Cite

View full text Add to dashboard Cite

A number of chronic airway diseases are characterized by high inflammation and unbalanced activation of the immune response, which lead to tissue damage and progressive reduction of the pulmonary function. Because they are exposed to various environmental stimuli, lung cells are prone to epigenomic changes. Many genes responsible for the immune response and inflammation are tightly regulated by DNA methylation, which suggests that alteration of the epigenome in lung cells may have a considerable impact on the penetrance and/or the severity of airway diseases. A major hurdle in clinical epigenomic studies is to gather appropriate biospecimens. Herein, we show that nasal epithelial cells are suitable to analyze DNA methylation in human diseases primarily affecting the lower airway tract.

show abstract

“…Much attention is, however, currently given to unravel epigenetic factors that influence CFTR gene expression. Results from studies on human embryonic stem cells show that histone modifications in the promoter may affect the regulation of CFTR expression, which warrants further investigation [70].…”

Section: Chronic Lung Diseasesmentioning

confidence: 97%