Theoretically, if the promoter region of a gene is highly methylated (hypermethylated), the transcription level should be low.
However, I notice that in many cases, when the RNA level of a gene is very high, its promoter region is heavily methylated.
Why??
Epigenetics and gene regulation are much more complicated and subtle than a simple "methylation = lower expression" sort of model.
One, most genes do NOT have a well-defined promotor.
Two, diploid organisms have two copies of every gene, which can show different methylation patterns.
Three, expression patterns are very tissue-specific and dynamic.
I suggest you do some background reading about epigenetics, gene expression and methylation patterns before jumping to any conclusions.
This is an interesting finding. Are you working with human genes with metabolic syndromes?
Perhaps it is highly methylated only on one allele while the other has considerably lower level of DNA methylation. PCR after bisulfite treatment can be biased. Do you have any chance to check at single alleles? I.e. using SNPs or other sequence variations?
There are several possible explanations for this, based on the fact that DNA methylation has numerous effects on gene expression. Arguably the most commonly studied is the disruption of DNA-binding protein motifs in the promoter. If the transcription factor recruits transcriptional activators, then methylation would suppress gene expression; however, if the transcription factor is a repressor, inhibiting its activity would actually induce gene expression.
other mechanisms of transcriptional regulation by methylation is its recruitment of histone complexes (PRC2/1 mediated), and these are also classically "bivalent" in their effects.
A relatively new realization is that the methods used to quantify DNA methylation also capture 5-hydroxymethylation, which is an hydroxylated form of the 5-methyldeoxycytidine that occurs during TET-mediated demethylation. So, you may be observing the active process of removing methylation from the promoter, thereby activating the associated gene.
Epigenetics and gene regulation are much more complicated and subtle than a simple "methylation = lower expression" sort of model.
One, most genes do NOT have a well-defined promotor.
Two, diploid organisms have two copies of every gene, which can show different methylation patterns.
Three, expression patterns are very tissue-specific and dynamic.
I suggest you do some background reading about epigenetics, gene expression and methylation patterns before jumping to any conclusions.
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