Methylome-wide analysis in systemic microbial-induced experimental periodontal disease in mice with different susceptibility

• Published in: Frontiers in cellular and infection microbiology Vol. 14; p. 1369226
• Main Authors: Hernandez Martinez, Cristhiam de Jesus, Glessner, Joseph, Finoti, Livia Sertori, Silva, Pedro Felix, Messora, Michel, Coletta, Ricardo Della, Hakonarson, Hakon, Palioto, Daniela Bazan
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 16-07-2024
• Subjects: Animals; Bacteroidaceae Infections - microbiology; Cellular and Infection Microbiology; differential methylome analysis; Disease Models, Animal; Disease Susceptibility; DNA Methylation; Epigenesis, Genetic; Epigenome; methylome; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; mouse models; periodontal disease; Periodontal Diseases - microbiology; Periodontitis - microbiology; Porphyromonas gingivalis; Porphyromonas gingivalis - genetics; Porphyromonas gingivalis; mouse models; DNA methylation; methylome; differential methylome analysis; periodontal disease
• ISSN: 2235-2988; 2235-2988
• DOI: 10.3389/fcimb.2024.1369226

The study delved into the epigenetic factors associated with periodontal disease in two lineages of mice, namely C57bl/6 and Balb/c. Its primary objective was to elucidate alterations in the methylome of mice with distinct genetic backgrounds following systemic microbial challenge, employing high-throughput DNA methylation analysis as the investigative tool.
(
)was orally administered to induce periodontitis in both Balb/c and C57bl/6 lineage. After euthanasia, genomic DNA from both maxilla and blood were subjected to bisulfite conversion, PCR amplification and genome-wide DNA methylation analysis using the Ovation RRBS Methyl-Seq System coupled with the Illumina Infinium Mouse Methylation BeadChip.
Of particular significance was the distinct methylation profile observed within the
-induced group of the Balb/c lineage, contrasting with both the control and
-induced groups of the C57bl/6 lineage. Utilizing rigorous filtering criteria, we successfully identified a substantial number of differentially methylated regions (DMRs) across various tissues and comparison groups, shedding light on the prevailing hypermethylation in non-induced cohorts and hypomethylation in induced groups. The comparison between blood and maxilla samples underscored the unique methylation patterns specific to the jaw tissue. Our comprehensive methylome analysis further unveiled statistically significant disparities, particularly within promoter regions, in several comparison groups.
The differential DNA methylation patterns observed between C57bl/6 and Balb/c mouse lines suggest that epigenetic factors contribute to the variations in disease susceptibility. The identified differentially methylated regions associated with immune regulation and inflammatory response provide potential targets for further investigation. These findings emphasize the importance of considering epigenetic mechanisms in the development and progression of periodontitis.