Saturday, November 17, 2012

The chemistry of DNA modifications for gene regulation

I have started learning about epigenetics, and particularly the regulatory effects of DNA methylation and histone acetylation. It's cool, it's hot, it's everything we hope will explain genetics, because genes certainly did not.

The chemistry behind this involves interesting pathways, involves storage of information that passes from one generation to another... epigenetic effects down to the grandchild generation have repeatedly been shown now. I likely candidate are mRNAs that persist beyond the cell division, which trigger modifications again. Well, that is cool chemistry indeed! So, the chemist in me asks: so where are residues actually methylated then? I am learning here, and trying to get the facts together. But, the bases seem to be one place, blocking interactions with DNA-binding proteins which can show beautiful residue/base pair interactions at the sides of the bases. Second year students at Maastricht University in Biomedical Sciences had this as part of their practical last year.

But for that genetic information to pass around and persist, and for gene regulation in general, there are brilliant pathways, which may involve metabolites, like butyrate, which acts as energy source in certain systems. Donohoe et al. report work around a pathway for histone acetylation, where they found an interaction with the Warburg effect. While in both cases butyrate triggers an increased acetylation, the mechanism is different. They propose this pathway, which I am making available on WikiPathways (CC-BY):

The page on WikiPathways is not complete yet, but I haven't completed reading the full paper yet. I wonder how many of these pathways are known. Do you know one? Leave a DOI/PubMed ID in the comments, or add the pathway to WikiPathways yourself.

ResearchBlogging.orgDonohoe, D., Collins, L., Wali, A., Bigler, R., Sun, W., & Bultman, S. (2012). The Warburg Effect Dictates the Mechanism of Butyrate-Mediated Histone Acetylation and Cell Proliferation Molecular Cell DOI: 10.1016/j.molcel.2012.08.033