Multiple correlation analyses revealed complex relationship between DNA methylation and mRNA expression in human...

Area of Science:

• Epigenetics and Genomics
• Molecular Biology
• Immunology

Background:

• DNA methylation is a key epigenetic mechanism regulating gene expression.
• The genome-wide relationship between DNA methylation and mRNA expression in human peripheral blood mononuclear cells (PBMCs) remains incompletely understood.
• Understanding these correlations is crucial for deciphering cellular regulatory mechanisms.

Purpose of the Study:

• To comprehensively explore the genome-wide correlation patterns between DNA methylation and mRNA expression in human PBMCs.
• To identify specific methylation sites and genes involved in regulating mRNA expression.
• To investigate the biological functions associated with genes under significant methylation-mRNA regulation.

Main Methods:

• Employed four distinct correlation analyses to assess the relationship between methylation levels and mRNA expression.
• Conducted genome-wide methylation-mRNA expression quantitative trait locus (eQTL) analysis in 46 unrelated female subjects.
• Utilized enrichment analysis to determine the biological functions of regulated genes.

Main Results:

• Observed moderate correlation intensity (rT1: -0.63-0.62) between methylation and mRNA, with nearly equal numbers of positive and negative correlations.
• Identified significant correlations in 60.1% of genes (PT4 < 0.05), with over 5.96% showing very strong correlations (RT4 > 0.8).
• eQTL analysis indicated methylation sites regulate mRNA expression, particularly near transcription start sites (TSS); regulated genes are enriched in essential cellular functions like transcription and translation.

Conclusions:

• DNA methylation exerts a complex and predictive regulatory effect on mRNA expression in PBMCs.
• The findings enhance understanding of methylation-mRNA correlations and provide valuable insights for future epigenetic research.
• Results offer clues for exploring biological and disease-related regulatory mechanisms within PBMCs.