The relationship between CpG island (CPGi) methylation and expression of the concerned gene depends on the region of the gene which has been methylated. CPGi methylation has primarily been studied in promoter regions and strong methylation in the promoter CPGi usually points towards a decreased expression of the gene. Few studies focusing on CPGi methylation in regions other than promoter are:
- Consider this report which talks about CPGi methylation of 3’UTRs and the increased expression of the genes: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6558231/
- Another report https://www.nature.com/articles/s41467-018-05550-5 talks about non-promoter CPGi in enhancer regions and gene body and they have been functionally associated with increased expression of the genes.
Thus while doing methylation analysis, it is important to narrow down to a region of interest. If one is interested in studying methylation in the promoter region, TSS serves as a good reference to select promoter region. Usually, +/- 2KB TSS region can be used to study promoter.
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