Dear Friend of CIFAR,

Crammed into the nucleus of every one of our cells is a lengthy 2 meters of DNA. When you consider that each cell measures a mere ten millionth of a meter across, this squeeze of our genetic blueprint for life is no small feat. In each cell, the genome is meticulously bundled, arranged into a complex assortment of loops and coils, like a really long, well-tied shoelace.

This packaging creates “silent DNA” – regions of the genome hidden from the action and basically turned off. Since the most important business of a cell depends on active genes, the Silent DNA limits what a cell can do.

How exactly does genome packaging control the amount of silent DNA? That’s what I’m on a quest to figure out.

My research group develops computational models that investigate how genome packaging helps turn our genes on or off. Protein complexes called nucleosomes are key players in this process. In a manner that’s both art and function, our DNA packs around nucleosomes to form compact chromosomes that resemble a bundled up pearl necklace. Helping this process along are many regulator proteins encoded in our genome.

One class of regulatory proteins interact with insulator elements, parts of our genome that help position nucleosomes and cause loops to form in the DNA. This looping protects certain regions of the genome from the silent DNA.

In collaboration with Craig Hart, Emmanuel Kas and Olivier Cuvier, I am investigating protein called BEAF (pronounced beef) that regulates insulator elements. BEAF is found in promoters –regions of DNA located next to a gene that control its expression. By combining theory and experiment, we are developing a model for how BEAF works. What we’ve found is that BEAF helps its insulator elements link together, trapping  nucleosomes in place. This trapping action keeps silent DNA at bay and helps to control gene expression.

The story of BEAF continues to unfold – we are now trying to understand how BEAF regulates the looping of the packaged genome. Dr. Cuvier, for example, is working on a whole genome map of how BEAF and its associated factors package the genome. Through our collaboration, we expect to fully untangle how BEAF mediates the big squeeze of our genetic blueprint for life.

Best wishes from the frontiers of human knowledge.

Eldon Emberly
Scholar, Genetic Networks program
Canadian Institute for Advanced Research
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