In one of the most popular science fiction tv shows of all time, Doctor Who and his companions travel through time and space in the TARDIS, engaging in heroic adventures – sometimes with the very fabric of the universe at stake.
The classic question from Doctor Who is not “Where are we?”, but “When are we?” This is the same question a gene must continually asks itself. Location follows – existing as part of that “when” answer. Consider…within a developing embryo skin cell…or within an adult brain cell forming a memory, etc. Now, what ways do genes have to help identify when to function? Epigenetic states, of course!
The Cell perspective, DNA Demethylation Dynamics, September 16th, 2011 is a must read! The authors Nidhi Bhutani, David M Burns and Helen M. Blau – are from the Stanford University system. Their paper provides a survey, and insightful commentary, on the identified enzymatic regulators and modification states of DNA methylation.
While presenting the available evidence, they postulate how DNA methylation states are dynamic , bidirectional, and can even be rapidly reversed. Of keen interest, 5hmC is an intermediate between methylation and demethylation states – but it doesn’t function to reactivate silenced genes. Rather, it actually correlates with inactive or non-productive promoters. Yet 5hmC must have separate functions from 5mC, given its pattern divergence in many instances.
Regenerative medicine researchers in particular, have a stake in determining the detailed mechanisms and defining the functional roles of methylation states – partially so that stable differentiation of cells can be controlled. Both iPSCs and nuclear transfer into oocytes, demonstrate that cellular fate can be reversible. The authors point out that regulation of methylation must be ongoing, in both active and stable cell states – but how exactly does this temporal and spatial functioning of genes take place?
These authors specifically note that newly available tools “will undoubtedly enhance our understanding of the complex relationship between cytosine methylation and demethylation, as well as the new roles for cytosine hydroxymethlation and deamination.”
Research opportunity knocks.
Bhutani N, Burns DM, & Blau HM (2011). DNA demethylation dynamics. Cell, 146 (6), 866-72 PMID: 21925312