Correct establishment of DNA methylation patterns is essential in development and required for silencing retrotransposons. In 2010, we published one of the largest databases of human DNA methylation data at that point (Edwards et al. 2010). Analyses of this data supported the hypothesis that the entire genome, including all transposable elements, was targeted for methylation, but that certain regions such as CpG islands were protected from this mechanism likely by histone modifications. More recent work as identified the protein Fbxl10 as being critical for the protection of a subset of CpG islands from methylation (Boulard et al 2015, 2016) and a role for OGT in mediating methylation-based repression of retrotransposons (Boulard et al. 2020).
Selected Relevant Publications
Boulard M, Rucli S, Edwards JR, Bestor TH. Methylation-directed glycosylation of chromatin factors represses retrotransposon promoters. Proc Natl Acad Sci U S A. 2020 Jun 23;117(25):14292-14298. doi: 10.1073/pnas.1912074117. Epub 2020 Jun 10. PubMed PMID: 32522876; PubMed Central PMCID: PMC7322000.
Boulard M, Edwards JR, Bestor TH. Abnormal X chromosome inactivation and sex-specific gene dysregulation after ablation of FBXL10. Epigenetics Chromatin. 2016;9:22. doi: 10.1186/s13072-016-0069-1. eCollection 2016. PubMed PMID: 27252784; PubMed Central PMCID: PMC4888662.
Boulard M, Edwards JR, Bestor TH. FBXL10 protects Polycomb-bound genes from hypermethylation. Nat Genet. 2015 May;47(5):479-85. doi: 10.1038/ng.3272. Epub 2015 Apr 6. PubMed PMID: 25848754.
Edwards JR, O’Donnell AH, Rollins RA, Peckham HE, Lee C, Milekic MH, Chanrion B, Fu Y, Su T, Hibshoosh H, Gingrich JA, Haghighi F, Nutter R, Bestor TH. Chromatin and sequence features that define the fine and gross structure of genomic methylation patterns. Genome Res. 2010 Jul;20(7):972-80. doi: 10.1101/gr.101535.109. Epub 2010 May 20. PubMed PMID: 20488932; PubMed Central PMCID: PMC2892098.