Methylation of distal regulatory elements like the Enhancers may also play a role in gene regulation (e.g IGF2/H19 imprinting regulation).

Recent studies (PMID: 28334074, PMID: 29958539) are also pointing to the importance of intragenic methylation in gene expression regulation.

It is important however to note that, a lot of times, genes are regulated by not just a single epigenetic mechanism like DNA methylation but a combination of them (e.g, histone methylation, chromatin packaging and sncRNA).

I hope this helps!

Hi,

the title of your question is different to the text as it states "non-CpG methylation" (methylation of cytosins not in the sequence context CG). Such methylation exist but mainly in stem cells. If you are more interested in methylation of CpGs outside from CpG islands (as your text states) then I would answer the following: Such methylation can certainly affect gene expression. However, the mechanism is maybe different. In general you can differentiate between effects of regional hypermethylation (i.e. CpG islands and regions with higher CpG density; methylation affecting histone modifications and chromatin condensation) and sequence specific effects (specific CpGs in a sequence context; methylation affecting transcription factor binding etc.). Both mechanism may exist also combined. In your case I would recommend to analyse the promotor sequence for the presence of transcription factor binding sites containing CpGs pointing to a epigenetic regulation of the TF binding. Depending on available data (Illumina bead-based arrays? 450K?) you may be able to identify specific CpGs which regulate gene expression.

Best,

Norman

To my knowledge, there are two main ways in which CpG methylation can regulate gene expression.

One of them is by "blocking" the promoter region of the gene in question. The transcription machinery is not able to attach to methylated DNA, thus the gene remains "silenced".

The other option is through chromatin condensation. CpG methylation can be recognized by epigenetic machinery leading to chromatin rearrangements that will eventually turn open (transcriptionally "active") chromatin into condensed (transcriptionally repressed) chromatin.

I don't know exactly how many methylated CpGs are required to block the transcription machinery from making its job neither how many are required to induce chromatin rearrangements through epigenetic machinery. However, I've seen some reports in which methylation of single CpGs could lead to gene silencing. It will depende on the site in which the methylated CpG is found within the DNA sequence. So i´ll think that there could be gene silencing through methylation of some CpGs even when they are not densely packaged within a short sequence of DNA to be considered an island CpG.

To give a more accurate answer to your question, you need to give us more information regarding the analysis that you made with Xenabrowser.