Perinatal inflammation alters histone 3 and histone 4 methylation patterns: Effects of MiR-29b supplementation

Preterm birth is still a major health problem and maternal inflammation has been shown to play a role. The combination of maternal inflammation and neonatal hyperoxia contributes to epigenetic changes that influence gene expression and the development of bronchopulmonary dysplasia (BPD). We have previously demonstrated suppression of miR-29b and increases in DNA methylation in infants with severe BPD and in our mouse model of maternal inflammation and neonatal hyperoxia exposure. The present studies further explored epigenetic changes in the murine model to include histone methylation. We identified a global suppression of histone methylation in exposed mice and validated decreases in expression in well-defined histone modifications, specifically H3K4me3, H3K27me3, H3K36me2, H3K79me2, and H4K2Ome3. We further tested the hypothesis that restoration of miR-29b expression would restore the histone methylation marks. Using lipid nanoparticle delivery of miR-29b, partial to full methylation was reestablished for H3K4me3, H3K27me3, and H4K2Ome3; all trimethylation marks. To identify the causes of decreased methylation in exposed mice, we measured commonly identified methylases and demethylases. We found a decreased expression of SUV40H2, a methylase primarily associated with H4K2Ome3. Further studies are needed to identify the causes for the decreased global histone methylation and potential therapeutic opportunities.

Automated summary

The study found that the combination of maternal inflammation and neonatal hyperoxia could lead to epigenetic changes that affect gene expression and the development of bronchopulmonary dysplasia. Histone methylation was found to be globally suppressed in exposed mice, and restoration of miR-29b expression reestablished methylation marks. Further research is needed to explore the causes of decreased global histone methylation and potential therapeutic opportunities.