A complex association between DNA methylation and gene expression in human placenta at first and third trimesters

Area of Science:

• Reproductive Biology
• Epigenetics
• Genomics

Background:

• The human placenta is crucial for fetal development and maternal health, undergoing significant changes during pregnancy.
• Previous research indicates epigenetic and gene expression alterations in the placenta throughout gestation.
• A comprehensive understanding of how DNA methylation impacts gene expression globally in the human placenta is lacking.

Purpose of the Study:

• To investigate global DNA methylation and gene expression changes in the human placenta from the first to the third trimester.
• To explore the relationship between DNA methylation patterns and gene expression levels in placental tissues.
• To elucidate the complexity of epigenetic regulation in human placenta development.

Main Methods:

• DNA methylome analysis using reduced representation bisulfite sequencing (RRBS).
• Gene expression profiling via RNA-sequencing (RNA-Seq).
• Comparative analysis of placental tissues from the first and third trimesters.

Main Results:

• Significant differential methylation observed in 199 promoters and 2,297 gene bodies between trimesters, predominantly hypermethylation.
• 2,447 differentially expressed genes identified, with a majority (77.2%) showing down-regulation.
• Gene Ontology analysis revealed enrichment for cell cycle and immune response functions among differentially expressed genes.
• The correlation between DNA methylation and gene expression was complex and non-linear, varying by genomic context and expression level.

Conclusions:

• Epigenetic regulation of human placenta development is intricate, involving complex, non-linear associations between DNA methylation and gene expression.
• Widespread DNA methylation and gene expression changes occur throughout human pregnancy, impacting key biological processes.
• These findings provide novel insights into the dynamic epigenetic landscape of the human placenta.