Global DNA hypermethylation in down syndrome placenta

Area of Science:

• Genetics
• Epigenetics
• Developmental Biology

Background:

• Down syndrome (DS) results from trisomy 21, but the mechanisms linking the extra chromosome to over 80 phenotypes remain unclear.
• Understanding the epigenetic alterations in DS is crucial for deciphering its complex pathology.

Purpose of the Study:

• To investigate global DNA methylation patterns in Down syndrome.
• To explore the potential role of TET family genes and REST/NRSF in DS-associated epigenetic changes.
• To determine if DNA methylation perturbations are conserved and linked to DS phenotypes.

Main Methods:

• Reduced representation bisulfite sequencing (RRBS) at single base resolution was employed.
• Analysis was performed on Down syndrome placenta villi and adult peripheral blood leukocytes.
• Gene expression levels and promoter methylation status were correlated.

Main Results:

• Global DNA hypermethylation was identified across all autosomes in DS samples.
• Genes on chromosome 21 showed an average 53% increase in expression, while hypermethylated genes were downregulated.
• DNA methylation alterations were conserved and enriched for genes associated with DS phenotypes.

Conclusions:

• Global epigenetic changes, specifically DNA hypermethylation, occur early in Down syndrome development.
• These epigenetic perturbations are likely mediated by altered DNA demethylation and transcriptional regulation pathways.
• The findings suggest a significant contribution of epigenetic dysregulation to the diverse phenotypes observed in Down syndrome.