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Genome-wide Analysis using ChIP to Identify Isoform-specific Gene Targets
Published on: July 8, 2010
Functional characterization of the atopy-associated gene PHF11
Emily Clarke1, Nusrat Rahman, Natalie Page
1Institute for Immunology and Allergy Research, Westmead Millennium Institute, University of Sydney, Westmead, Australia.
The Journal of Allergy and Clinical Immunology
|April 15, 2008
Summary
Plant homeodomain finger protein 11 (PHF11) regulates T(H)1 cytokine gene expression. Genetic variations linked to atopic dermatitis (AD) reduce PHF11, potentially driving allergic T(H)2 responses.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- Plant homeodomain finger protein 11 (PHF11) gene polymorphisms are linked to elevated IgE, asthma, and atopic dermatitis (AD).
- The functional role of PHF11, despite its transcriptional regulator-associated domain, remains largely uncharacterized.
Purpose of the Study:
- To investigate if PHF11 modulates the transcription of genes implicated in allergic diseases.
- To determine if PHF11 polymorphisms influence its expression or functional activity.
Main Methods:
- Microarray analysis to assess PHF11 expression in immune cell subsets.
- RNA interference (RNAi) and overexpression studies in CD4+ T cells and Jurkat T cells to evaluate PHF11 function.
- Allele-specific gene expression, luciferase reporter assays, and electrophoretic mobility shift assays (EMSAs) to assess genotype-dependent effects and transcriptional activity.
Main Results:
- PHF11 expression is higher in T(H)1 cells compared to T(H)2 cells.
- PHF11 knockdown decreased T(H)1 cytokine (IFN-gamma, IL-2) expression.
- An AD-associated single nucleotide polymorphism (SNP) correlated with reduced PHF11 RNA and an altered PHF11 isoform.
- Physical and functional interaction identified between PHF11 and nuclear factor kappaB (NF-κB) p65 subunit.
Conclusions:
- PHF11 acts as a critical regulator of T(H)1-type cytokine gene expression.
- Reduced PHF11 expression due to specific genotypes may predispose individuals to T(H)2-dominant allergic responses characteristic of AD.
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