The impact of DNA methylation of different regions?

Question

[-IvanWoo-]

Hello, community,

When I perform DNA methylation data processing and analysis (WGBS), I follow the current consensus and compare the methylation levels of the gene promoter region (2kbp), and thus speculate on the expression regulation of the gene. However, my supervisor asked me last week, "Does DNA methylation only work in the promoter region? Why only focus on the promoter methylation level?"

I can't come up with a reasonable explanation. When I looked up relevant studies, I did find reports on methylation of gene body regions. Ref From the results, it seems more significant that the gene body region of highly expressed genes will have ultra-high levels of methylation. In contrast, in the promoter region, there will be no obvious difference in methylation levels.

I also found the research conclusions referenced by this study, and the results are similar. From these results, it seems that CpG methylation in the gene body region cannot be ignored.

Does anyone know how to explain it or give some ideas for discussion?

[Matthias Zepper]

Technically, this is not a bioinformatics question, but since I worked in the field of DNA methylation before dropping out of active research in 2019, I have a couple of references / reading recommendations that I can share nonetheless:

• Body-hypomethylated human genes harbor extensive intragenic transcriptional activity and are prone to cancer-associated dysregulation
• Replication timing-related and gene body-specific methylation of active human genes
• Dynamic DNA methylation: In the right place at the right time

For anything after 2019, you have to search the literature yourself.

[-IvanWoo-]

Thanks for the information you provided. My intuitive feeling after reading is that there is currently no conclusion on the impact of CpG methylation in the genebody region. Am I understanding correctly?