A physical and functional interaction between two epigenetic enzymes
Epigenetic mechanisms refer to heritable changes in phenotype that are not encoded in the DNA sequence. For example, differences between identical twins that cannot be explained by their environment can potentially arise from epigenetic effects. Epigentics is important in animal and plant development and increasingly found to be a factor in human disease.
While in Gerard Cagney's lab, Ariane Waston (now a Senior Researcher with Colm Ryan at Systems Biology Ireland), worked on epigenetic protein interactions for her PhD. Based on this work, a paper just published in Molecular Cell describes how an enzyme complex normally involved in turning off genes - Polycomb Repressor Complex 2 - interacts with another enzyme (NSD1) that is associated with active transcription.
Both enzymes are responsible for methylation of histone proteins, but at distinct lysine residues. Patterns of methylation, acetylation, and other modifications on histones are believed to regulate expression of the nearby genes - these patterns are sometimes referred to as the 'histone code'. The rules that govern this code are only partly understood, so it was intriguing to find the products of two enzymes with apparently opposing functions together on the genome.
One outstanding question is how regions of the genome that are regulated by Polycomb are insulated from other regions. In a collaboration involving Gundula Streubel, Adrian Bracken's lab at Trinity College, Diego Pasini at the European Institute of Oncology in Milan, Nevan Krogan at the Gladstone Institute in San Francsico, and members of the Conway Institute Mass Spectrometry Core, Ariane showed that the interaction of these two enzymes is involved in generating and maintaining these boundaries. Since both enzymes are strongly implicated in cancer and other diseases, the findings may also be relevant to understanding disease mechanism and developing new therapeutic approaches.
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