The blueprint for cellular potential is written out in DNA, encoding thousands of genes that all have the potential to be expressed as functional gene-products, such as proteins and enzymes. To a great extent, the popular understanding of DNA research was that sequencing the complete human genome would unlock secrets to the limits of our physical potential and newfound power over longevity and disease.

However, we are becoming increasingly aware of our epigenomes — the mechanisms that govern the expression of the genes written into DNA — and the power they hold over our development. The Epigenetics Research Theme was organized in the Wisconsin Institute for Discovery to explore the checks on gene activation.

The epigenome consists of a complex array of specific chemical “marks” on chromatin (DNA-protein complex), which alters the packaging of DNA and dynamically controls gene expression. DNA is spooled around histone proteins, forming nucleosomes, which assist in the compaction of huge amounts of DNA into tiny cell nuclei. Subtle differences in the wrapping, combination and placement of chemical markers on DNA and histones govern when and how often genes are read. Misalignment or misinterpretation of the resulting code prevents normal gene activation and appears to play a role in developmental disorders, the aging process and numerous diseases — including many forms of cancer.

While DNA remains rigid, epigenomes have proven to be malleable and open to influence by outside forces. Alter the diet of female mice, and the changes will echo through their offspring as differences in the way chromatin arranges and marks DNA — and thus emphasizes, mutes or even blots out the expression of certain genes in successive generations of mice.

Research describing the effects of epigenetic differences is piling up at a dizzying rate, but how the epigenetic code is written, erased and interpreted is poorly understood. Led by UW-Madison biomolecular chemistry professor John Denu, the Wisconsin Institute for Discovery’s epigenetics research theme was organized to address those challenges through a focus on the molecular, chemical and physical basis underlying epigenetic mechanisms and how they may predispose some people to certain diseases.

We intend to tap the University of Wisconsin-Madison’s strength in related disciplines — fundamental investigations of DNA transcription processes, stem cell biology and epigenetics-controlled diseases such as cancer — and the presence in Madison of private companies developing epigenetics tools to foster collaborations that aid in the pace and scope of epigenetics research.