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Published on: September 7, 2017
Chromosome-wide DNA methylation analysis predicts human tissue-specific X inactivation
Allison M Cotton1, Lucia Lam, Joslynn G Affleck
1Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
Human Genetics
|May 21, 2011
Summary
X-chromosome inactivation (XCI) epigenetic marking differs between males and females, with promoter methylation accurately predicting XCI status in blood. Tissue-specific XCI was observed in 12% of genes, highlighting epigenetic plasticity.
Area of Science:
- Epigenetics
- Genomics
- Molecular Biology
Background:
- X-chromosome inactivation (XCI) involves differential epigenetic marking of X chromosomes.
- CpG island promoters of XCI genes are differentially methylated between sexes.
Purpose of the Study:
- To investigate X-chromosome methylation patterns in blood and across tissues.
- To predict XCI status using DNA methylation differences between sexes.
- To explore the relationship between gene expression and gene-body methylation.
Main Methods:
- Chromosome-wide Methylated DNA ImmunoPrecipitation (MeDIP).
- Promoter-targeted methylation analysis using Illumina Infinium HumanMethylation27 array.
- Comparison with previously published gene expression data.
Main Results:
- Largest methylation differences between sexes found at X-linked CpG island promoters.
- Methylation-based prediction of XCI status in blood showed 81% concordance with expression data.
- 83% of genes exhibited consistent XCI status across tissues; 12% showed tissue-specific XCI.
- Highly expressed genes had more methylated X-linked introns, but exonic methylation was independent of expression.
Conclusions:
- Promoter CpG island methylation effectively predicts XCI status.
- A significant subset of X-linked genes displays tissue-specific XCI.
- Gene-body methylation patterns are influenced by transcription levels, particularly in introns.
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