Protein-DNA Research Adds Insights for Human Genetics
Research led by a graduate student at the University of Tennessee, Knoxville, revealed an unexpected molecular mechanism in gene transcription.
The study published in Science Advances with lead author David P. Lohry (PhD ’24) focused on a nuclear hormone receptor, thyroid receptor-α (TRα), and found both functional and structural changes when bound to DNA. Nuclear hormone receptors are proteins that directly regulate the transcription of genes that control a wide variety of biological processes, including cell proliferation, development, metabolism, and reproduction.
The research is part of a longtime collaboration in the UT Department of Biochemistry and Cellular and Molecular Biology between two laboratories. Associate Professor Elias Fernandez’s lab is focused on studying the mechanisms of nuclear receptors that control the specificity of gene transcription, with a goal of predicting the genome-scale effects of specific treatment regimens. Associate Professor Tongye Shen’s lab specializes in using advanced computational tools to understand molecular and cellular biosystems.
“Since working with disordered proteins is experimentally tricky, Fernandez and I knew we could utilize computational modeling to strengthen our research alongside my benchtop experiments,” Lohry explained. “With assistance from the Shen Lab, I was able to run my own computational simulations which complemented the biophysical and genomics studies.”
The discovery advances the understanding of gene transcription and regulation, and suggests further study into disordered regions in proteins binding to DNA as part of disease research.
The research reveals a mechanism that extends beyond this family of proteins, broadly impacting other proteins that affect the critical regulation of gene activity and genome organization.
By Amy Beth Miller