Chief Architects Guiding Epigenetic Switching of Genes Identified

In a breakthrough discovery that could open up whole new possibilities in fighting cancer, researchers now discovered the control mechanism that dynamically reprograms our genome. A study by Yale School of Medicine researchers pinpoints the molecular regulators of epigenetics - the still obscure process by which unchanging genes along our DNA are switched on and off at precisely the right time and place.

They write that "if a genome is the blueprint for life, then the chief architects are tiny slices of genetic material that orchestrate how we are assembled and function".

The mechanism, discovered over the past 20 years, is based on certain proteins--called epigenetic factors--that traverse the static genome and turn single genes on or off. The extreme number of potential combinations of active and inactive genes explains why a relatively small number of genes can carry out such a wide range of functions.

But what controls and guides these epigenetic factors to their target? The answer, the Yale team has found, is specialized RNAs called piRNAs.

"This is the first major mechanism discovered that controls where epigenetic factors - the gene switches - are to be placed in the genome," said Haifan Lin, director of the Yale Stem Cell Center and senior author of the study.

The Yale team analyzed the genome of the fruit fly Drosophila in their latest study, and discovered that piRNAs guide epigenetic factors to numerous sites throughout the genome, where these switches work to turn genes on or off. The dramatic change in gene expression patterns found illustrated piRNAs key role in coordinating biological activity.

Several types of cancers are already thought to be triggered when the wrong kinds of piRNAs guide epigenetic factors to activate the wrong genes, which seems to make perfect sense, similar to a serious programming error and resulting bugs. Blocking the action of these piRNAs should become a new opportunity to treat cancers, Lin said.

Study:

Xiao A. Huang et al., A Major Epigenetic Programming Mechanism Guided by piRNAs, Developmental Cell, 2013, DOI: 10.1016/j.devcel.2013.01.023