Can methylation of a promoter induce gene expression in some rare cases?

Question

Can methylation of a promoter induce gene expression in some rare cases? I've read somewhere that methylation of an intron can induce gene expression (eg. Igf2). How is that even possible? Thank you in advance!

Answer 1

In short yes, and so you know, epigenetic changes to the genome are not as rare as you may believe. In the context of histone methylation (which I am more familiar with as it is a subject of my research) acts as a signal or marker that is indispensable to differentiation and function of various cell types. Fort instance, it is a generally accepted that histone arginine-methylation acts as an activation marker, which induces opening of chromatin which allows for subsequent activation.

An example of this from a 2017 paper has shown how histone arginine methylation at the promoter site of PPARg actually expression by recruiting TFs to the promotor and is required for alternative activation of macrophages in response to infection. This is one specific example of many that are out there. Methylation can also act on transcription factors to modulate their activity. There are also instances of direct DNA methylation at CpG islands that can not only regulate gene expression by opening/closing of chromatin, but by also cause large architectural changes that can bring enhancer regions to promotor sites that Kilo- or even Mega-bases away !

Answer 2

Well maybe if it is a promoter that ends up creating a regulatory protein in another pathway.