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Disease-Associated MRNA Expression Differences in Genes with Low DNA Methylation
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- Barrenäs, Fredrik (författare)
- Linköpings universitet,Institutionen för klinisk och experimentell medicin,Hälsouniversitetet
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- Bruhn, Sören (författare)
- Linköpings universitet,Institutionen för klinisk och experimentell medicin,Hälsouniversitetet
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- Gustafsson, Mika (författare)
- Linköpings universitet,Institutionen för teknik och naturvetenskap,Tekniska högskolan
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- Jörnsten, Rebecka (författare)
- Mathematical Sciences, Chalmers University of Technology, University of Gothenburg, Gothenburg, Sweden
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- Langston, Michael A (författare)
- Department of Electrical Engineering and Computer Science, University of Tennessee, Knoxville, USA
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- Nestor, Colm (författare)
- Östergötlands Läns Landsting
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- Rogers, Gary (författare)
- Department of Electrical Engineering and Computer Science, University of Tennessee, Knoxville, USA
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- Wang, Hui (författare)
- Linköpings universitet,Institutionen för klinisk och experimentell medicin,Hälsouniversitetet
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- Benson, Mikael (författare)
- Linköpings universitet,Institutionen för klinisk och experimentell medicin,Hälsouniversitetet
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(creator_code:org_t)
- 2012
- Engelska.
- Relaterad länk:
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https://urn.kb.se/re...
Abstract
Ämnesord
Stäng
- Although the importance of DNA methylation for mRNA expression has been shown for individualgenes in several complex diseases, such a relation has been difficult to show on a genome-wide scale.Here, we used microarrays to examine the relationship between DNA methylation and mRNAexpression in CD4+ T cells from patients with seasonal allergic rhinitis (SAR) and healthy controls.SAR is an optimal disease model because the disease process can be studied by comparing allergenchallengedCD4+ T cells obtained from patients and controls, and mimicked in Th2 polarised T cellsfrom healthy controls. The cells from patients can be analyzed to study relations between methylationand mRNA expression, while the Th2 cells can be used for functional studies. We found that DNAmethylation, but not mRNA expression clearly separated patients from controls. Similar to studies ofother complex diseases, we found no general relation between DNA methylation and mRNAexpression. However, when we took into account the absence or presence of CpG islands in thepromoters of disease associated genes an association was found: low methylation genes without CpGislands had significantly higher expression levels of disease-associated genes. This association wasconfirmed for genes whose expression levels were regulated by a transcription factor of knownrelevance for allergy, IRF4, using combined ChIP-chip and siRNA mediated silencing of IRF4expression. In summary, disease-associated increases of mRNA expression were found in lowmethylation genes without CpG islands in CD4+ T cells from patients with SAR. Further studies arewarranted to examine if a similar association is found in other complex diseases.
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