A leader in the field of epigenetics is Andy Fienberg of Johns Hopkins University (Baltimore MD USA) 
who presented a talk at the European Society for Human Genetics 2014. Entitled “The epigenetic basis of common human disease”, he began by referring to his highly influential 2009 Nature Genetics paper, in which he gave evidence for functionally important CpG island methylation in colon tumor tissue up to 2kb away, which was termed ‘CpG island shores’.
This conserved hypo- and hyper-methylation in colon tumor tissue (called Cancer-specific DNA Methylation Region, or C-DMR) was also shown to be conserved in normal tissue (called Tissue-specific DNA Methylation Region, or T-DMR), and that this island shore methylation is strongly related to gene expression. Showing a figure from this paper (along with a photo of himself and Bert Vogelstein also at Hopkins from 30 years ago), it was a striking introduction to his work in epigenetics that spans decades.
Citing this work from Bert Vogelsteins’ group, he pointed out the limits of what we currently know about human genomics and its limitations (in particular the problem of ‘missing heritability’), only a maximum of 20% of the heritability of diseases and other phenotypes can be accounted for. This led him to share a story about how he was thinking of this problem while visiting the Westminster Abbey, where Charles Darwin is buried (along with Isaac Newton). His thought while musing in that location was an idea of the role of stochastic variation during development: could stochastic variation play a role during developmental processes? And could this variation extend to epigenetic modifications?
Looking at inbred mice strains, there are variable methylated regions between individuals. This dynamic landscape he believes has a random nature to it, regulated by nuclear structure (histone binding, higher order chromatin organization), but that is also deformable by processes such as tumor generation. Feinberg referred to this paper that suggests that higher epigenetic variation is associated with a key feature of tumorgenesis instability.
Dr. Feinberg finished by referring to a recent review in Nature that explores this idea of epigenetic and gene expression plasticity in further detail.
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