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NC State study finds epigenome proteins produce diverse gene expression patterns beyond simple on/off switching

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Study Reveals Epigenome Regulators Create Diverse Gene Expression Patterns

A new study from North Carolina State University has examined how proteins that interact with DNA influence gene expression, moving beyond the simple concept of genetic "on/off" switches.

"We already knew that the proteins in the epigenome control the way DNA is expressed. Our goal here was to look at a single gene and quantify the full range of ways that the gene could be expressed by different proteins." — Albert Keung, corresponding author and associate professor at NC State.

The Experiment

Researchers focused on a single gene from yeast and exposed it to 87 different epigenome regulator proteins. Each protein-gene interaction was tested in approximately 100 yeast cells using light-controlled binding, with real-time measurement over a 12-hour period.

"We designed this study in a way that allowed us to capture the dynamics of this entire process," explained co-first author Jessica Lee. "We could control and measure how long the protein was exposed to the gene and we could observe and measure the dynamic behavior of the gene in response to the protein."

Key Findings

  • Unique Patterns: Each protein produced a uniquely patterned response of gene expression, demonstrating functions far beyond simple on/off switching.
  • Consistency vs. Noise: Some proteins produced consistent gene expression patterns across all cells tested, while others produced variable responses with significant noise.
  • Functional Correlation: Gene expression patterns correlated with known protein functions. For example, proteins known to recruit polymerase produced similar patterns.
  • Modeling Success: A computational model using a three-state system with positive feedback was able to capture all experimental data.

"The big finding here was that each protein produced a uniquely patterned response of gene expression from the gene. The proteins are far more than an on/off switch." — Albert Keung

Co-first author Leandra Caywood provided examples: "For example, one protein may turn the gene on quickly; a second protein may take slightly longer to turn the gene on—but then keep it on for a long time; and a third protein might have a long time delay before turning the gene on, at which point it spikes up quickly and then turns off right away."

Implications and Applications

The findings have significant potential for advancing cellular engineering:

  • Biomanufacturing & Cell Therapies: Applications include the biomanufacturing of proteins or the development of cell therapies for pharmaceutical and biomedical sectors.
  • Fine-Tuning Production: Understanding protein-induced gene expression patterns could help scientists fine-tune protein production activities.
  • Optimizing Pathways: Proteins that produce random expression patterns could be useful for optimizing bioproduction pathways by testing various protein ratios.
  • Informed Engineering: The computational model provides insight into how proteins function, enabling more informed engineering decisions.

Publication and Funding

The study, "Epigenome Regulators Imbue a Single Eukaryotic Promoter with Diverse Gene Expression Dynamics," was published open access in the journal iScience.

Co-authors included Riley Basinger, Lucas Abbott, and Nicholas Levering from NC State.

Funding was provided by the National Institutes of Health under grants 5T32GM133366 and 5F31CA268873, and the National Science Foundation under grants 2144539 and 1830910.