Mattei, Bailly, and Meissner provide an insightful review of CpG methylation in Trends in Genetics, tracing from its discovery in 1925 to current knowledge and outstanding questions. Originally a defense mechanism in bacteria against bacteriophages, DNA methylation has evolved significantly.
What fascinates me most is the regulatory diversity of CpG methylation across the genome, which consists largely of two types of long domains: PMDs (partially methylated domains) and HMDs (highly methylated domains). Short de-methylated regions play critical roles:
– Near gene promoters in CpG islands, necessary for expression.
– In enhancer regions, where demethylation facilitates regulatory contact with transcription factors.
– At CTCF sites, where demethylation is essential for CTCF binding, influencing chromatin looping.
Conversely, methylation can silence genes, deactivate enhancers, and inhibit some chromatin loops. Interestingly, the gene bodies of actively expressed genes often show increased methylation.
Data scientists analyzing CpG methylation data need to identify PMDs, HMDs, and assess the methylation status of these key regions using appropriate genome annotations.
Mattei AL, Bailly N, Meissner A. DNA methylation: a historical perspective. Trends Genet. 2022 Jul;38(7):676-707. https://www.cell.com/action/showPdf?pii=S0168-9525%2822%2900071-3
#epigenetics #DNAmethylation
Jieun Jeong (정지은), Ph.D. 