Hyunjin Kim1,2, Fatemeh Momen-Heravi3, Steven Chen3, Per Hoffmann4, Moritz Kebschull3,5, Panos N Papapanou3. 1. Biomedical Informatics Shared Resource, Herbert Irving Comprehensive Cancer Center and Department of Systems Biology, Columbia University, New York, New York, USA. 2. Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. 3. Division of Periodontics, Section of Oral, Diagnostic and Rehabilitation Sciences, College of Dental Medicine, Columbia University, New York, New York, USA. 4. Institute of Human Genetics, University of Bonn, Bonn, Germany. 5. School of Dentistry, Institute of Clinical Sciences, University of Birmingham, Birmingham, UK.
Abstract
AIM: We investigated differential DNA methylation in gingival tissues in periodontal health, gingivitis, and periodontitis, and its association with differential mRNA expression. MATERIALS AND METHODS: Gingival tissues were harvested from individuals and sites with clinically healthy and intact periodontium, gingivitis, and periodontitis. Samples were processed for differential DNA methylation and mRNA expression using the IlluminaEPIC (850 K) and the IlluminaHiSeq2000 platforms, respectively. Across the three phenotypes, we identified differentially methylated CpG sites and regions, differentially expressed genes (DEGs), and genes with concomitant differential methylation at their promoters and expression were identified. The findings were validated using our earlier databases using HG-U133Plus2.0Affymetrix microarrays and Illumina (450 K) methylation arrays. RESULTS: We observed 43,631 differentially methylated positions (DMPs) between periodontitis and health, and 536 DMPs between gingivitis and health (FDR < 0.05). On the mRNA level, statistically significant DEGs were observed only between periodontitis and health (n = 126). Twelve DEGs between periodontitis and health (DCC, KCNA3, KCNA2, RIMS2, HOXB7, PNOC, IRX1, JSRP1, TBX1, OPCML, CECR1, SCN4B) were also differentially methylated between the two phenotypes. Spearman correlations between methylation and expression in the EPIC/mRNAseq dataset were largely replicated in the 450 K/Affymetrix datasets. CONCLUSIONS: Concomitant study of DNA methylation and gene expression patterns may identify genes whose expression is epigenetically regulated in periodontitis.
AIM: We investigated differential DNA methylation in gingival tissues in periodontal health, gingivitis, and periodontitis, and its association with differential mRNA expression. MATERIALS AND METHODS: Gingival tissues were harvested from individuals and sites with clinically healthy and intact periodontium, gingivitis, and periodontitis. Samples were processed for differential DNA methylation and mRNA expression using the IlluminaEPIC (850 K) and the IlluminaHiSeq2000 platforms, respectively. Across the three phenotypes, we identified differentially methylated CpG sites and regions, differentially expressed genes (DEGs), and genes with concomitant differential methylation at their promoters and expression were identified. The findings were validated using our earlier databases using HG-U133Plus2.0Affymetrix microarrays and Illumina (450 K) methylation arrays. RESULTS: We observed 43,631 differentially methylated positions (DMPs) between periodontitis and health, and 536 DMPs between gingivitis and health (FDR < 0.05). On the mRNA level, statistically significant DEGs were observed only between periodontitis and health (n = 126). Twelve DEGs between periodontitis and health (DCC, KCNA3, KCNA2, RIMS2, HOXB7, PNOC, IRX1, JSRP1, TBX1, OPCML, CECR1, SCN4B) were also differentially methylated between the two phenotypes. Spearman correlations between methylation and expression in the EPIC/mRNAseq dataset were largely replicated in the 450 K/Affymetrix datasets. CONCLUSIONS: Concomitant study of DNA methylation and gene expression patterns may identify genes whose expression is epigenetically regulated in periodontitis.
Authors: Panos N Papapanou; Mariano Sanz; Nurcan Buduneli; Thomas Dietrich; Magda Feres; Daniel H Fine; Thomas F Flemmig; Raul Garcia; William V Giannobile; Filippo Graziani; Henry Greenwell; David Herrera; Richard T Kao; Moritz Kebschull; Denis F Kinane; Keith L Kirkwood; Thomas Kocher; Kenneth S Kornman; Purnima S Kumar; Bruno G Loos; Eli Machtei; Huanxin Meng; Andrea Mombelli; Ian Needleman; Steven Offenbacher; Gregory J Seymour; Ricardo Teles; Maurizio S Tonetti Journal: J Clin Periodontol Date: 2018-06 Impact factor: 8.728
Authors: F Momen-Heravi; R A Friedman; S Albeshri; A Sawle; M Kebschull; A Kuhn; P N Papapanou Journal: J Dent Res Date: 2021-01-08 Impact factor: 6.116
Authors: Eugene Y Chiang; Tianbo Li; Surinder Jeet; Ivan Peng; Juan Zhang; Wyne P Lee; Jason DeVoss; Patrick Caplazi; Jun Chen; Søren Warming; David H Hackos; Susmith Mukund; Christopher M Koth; Jane L Grogan Journal: Nat Commun Date: 2017-03-01 Impact factor: 14.919