Genes can be silenced by multiple methylation of CpG sites in the CpG islands of their promoters.[11] Even if silencing of a gene is initiated by another mechanism, this often is followed by methylation of CpG sites in the promoter CpG island to stabilize the silencing of the gene.[11] On the other hand, hypomethylation of CpG islands in promoters can result in gene over-expression.
Causes of DNA hypermethylation  are:
- Mediation of mutated K-ras induced jun protein (Serra RW. et al. 2014; Leppä S. et al. 1998)
- the inhibitory effect of lnRNA on miRNAs causing demethylation - their "absorption" in the sponge effect or direct repression of demethylation factors TET1 and TGD (Thakur S. Brenner C. 2017; Ratti M. et al. 2020; Morita S. et al. 2013)
- Activation of DNA methylases (Kwon JJ. et al. 2018)
- Changes in isocitrate dehydrogenase (Christensen BC. et al. 2011)
- Effects of viruses (Wang X. et al. )
 Causes of DNA hypomethylation:
- The effect of mutated K-ras on long non-coding RNAs, which, when acting, a) directly inhibits the activity or translation of genes encoding DNA methylases (Sarkar D. et al. 2015) b) rather, "sponges" absorb miRNAs (Ratti M. et al. 2020 ), which should ensure the functioning of DNA methylases
- The effect of mutated K-Ras through the activation of the myc-ODC axis, the mTor complex, with the consequence of the synthesis of polyamines, the activation of which, figuratively speaking, "pumps out" single-carbon fragments from the Methionine cycle and creates a lack of substrate for DNA methylation, leading to a hypomethylated state of DNA (Урба К. 1991 )
- Changes in the activity of methylases DNMT1/3A/3B, their relocalization (Hoffmann MJ, Schulz WA. 2005; Nishiyama A. et al. 2021)
- Changes in TET performance (Nishiyama A. et al. 2021)
- Changes in the synthesis of SAM from methionine due to changes in the enzymes MAT (Frau M. et al. 2013)
- Changes in serine catabolism (Snell K., Weber G. 1986), causing more intensive removal of homocysteine from the methionine cycle, when serine binds to homocysteine (Урба К. 1991)
- Other, unspecified reasons for supplying the Met cycle with single-carbon fragments, causing e.g. "methyl trap" phenomenon (Shane B. Stokstad EL. 1985; Zheng Y, Cantley LC. 2019), sietin and with disorders of vitamin B12 metabolism, disruption of the spare methionine resynthesis pathway (Ouyang Y. et al. 2020; Ozyerli-Goknar E, Bagci-Onder T. 2021; Barekatain, Yasaman et al. 2021) or other monocarbon fragment metabolism disorders (Urba K. 1991).