Albany 2015:Book of Abstracts
June 9-13 2015
©Adenine Press (2012)
Evolving insights on how cytosine methylation affects protein-DNA binding
Many anecdotal observations exist of a regulatory effect of DNA methylation on gene expression (Dantas Machado et al., 2015). However, in general, the underlying mechanisms of this effect are poorly understood. Cytosine methylation can abrogate or enhance interactions with DNA-binding proteins, or it may have no effect, depending on the context. Despite being only a small chemical change, the addition of a methyl group to cytosine can affect base readout via hydrophobic contacts in the major groove and shape readout via electrostatic contacts in the minor groove. Additionally, 5-methylcytosines change the stability of nucleosomes and, thus, affect the local chromatin structure and access of TFs to genomic DNA. Given these complexities, it seems unlikely that the influence of DNA methylation on protein-DNA binding can be captured in a small set of general rules. Hence, data-driven approaches may be essential to gain a better understanding of these mechanisms. DNase I bias towards the methylated recognition motif has been explained by changes in structural features induced by CpG methylation in the binding site (Lazarovici, A., et al., 2013). In order to understand the role of DNA methylation on DNA shape readout we have designed a high-throughput method, which can facilitate the user with structural profiles of methylated vs. unmethylated DNA. Differences between the two profiles can help us better understand the role of DNA methylation in vivo. To this end, we have used minor groove width, propeller twist, roll, and helix twist as the structural parameters.,
Lazarovici, A., et al., Probing DNA shape and methylation state on a genomic scale with DNase I. Proc Natl Acad Sci U S A, 2013. 110(16): p. 6376-81.
1Molecular and Computational Biology Program