3D Map of Mouse Genome Sheds Light on Retinal Development

St. Jude Children's Research Hospital scientists have created a 3D map of a mouse genome.

"Understanding the way cells organize their genomes during development will help us to understand their ability to respond to stress, injury and disease," said Michael Dyer, Ph.D., one of the corresponding authors of the paper that appeared in Neuron today.

The research focused on light-sensing rod cells in the mouse retina. More than 8,000 genes are turned on or off during retinal development. Thousands of regulatory regions across the genome also play a role. Researchers used ultra-deep chromosome conformation capture or Hi-C analysis to map those interactions in mouse rod cells.

Using integrated analysis of data from a variety of sources and machine learning, investigators showed genomic organization changed in surprising ways at different stages of development. "These changes are not random, but part of the developmental program of cells," Dyer said.

The study was able to capture long-distance interactions between promoters and enhancers at different stages of retinal development. Researchers also tracked changes in genome organization during development. That included using machine learning to gauge how easily accessible genes are for transcription.

The research also reported on a powerful regulator of gene expression, a super enhancer that worked in a specific cell at a specific stage of development. They found that when a core regulatory circuit super-enhancer for the Vsx2 gene was deleted, an entire class of neurons (bipolar neurons) was eliminated. No other defects were identified. Deletion of the Vsx2 gene causes many more defects in retinal development so the super-enhancer is highly specific to bipolar neurons.