A roadmap for gene regulation in plants

For the first time, researchers at the Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab) have developed a genome-scale method to map the regulatory role of transcription factors, proteins that play key roles in gene expression and in the determination of physiological traits of plants. Their work reveals unprecedented insights into genetic regulatory networks and identifies a new library of DNA parts that can be used to optimize genetic engineering efforts in plants.

Headshot of Niklas Hummel, a person with short brown hair wearing a white shirt, photographed in front of green leaves.

Niklas Hummel (Image courtesy of Niklas Frederik Christopher Hummel)

Transcription factors regulate things like how plants grow, how much fruit they produce and what their root architecture looks like, said Niklas Hummel, lead author of a study on the research in the journal cellular systems and research associate at the Department of Energy’s Joint BioEnergy Institute (JBEI), run by the Berkeley Lab. By deciphering their regulatory role, we can identify new strategies for designing more drought-tolerant bioenergy crops and other plants with improved agronomic characteristics.

Hummel and senior study author Patrick Shih, a Berkeley Labs Biosciences Area faculty scientist and director of plant biosystems design at JBEI, set out to develop a method to characterize a large number of transcription factors in a plant at once. While there are methods to do this for other model organisms, such as animals, insects and fungi, applying them to plants has been challenging, due to their complexity and the destructive presence of cell walls.

To date, these kinds of studies have really been done piecemeal in plants, where we only understood the function of a particular transcription factor because a group of researchers focused on it for many years, said Shih, who is also a researcher at the Innovative Genomics Institute. So what we’ve been trying to do instead is find a way to map the activity of hundreds of these transcription factors in a plant at the same time.

To address this challenge, Hummel and Shih employed a transient expression system they had previously developed to build synthetic biology tools in plants. Here, they used the system to characterize, in parallel, a network of over 400 transcriptional effector domains in the tobacco plant Nicotiana benthamianaa feat never before achieved in synthetic plant biology.

A figure made up of many circles connected to each other by lines, all tangled with each other.  The circles range in color from red, which indicates activator, to white, which indicates minimally active, to blue, which indicates repressor.  At the bottom of the figure reads the text: Genome-scale network based on DNA binding and effector activity data.

Studying the potential of hundreds of plant transcription factors to turn genes on and off allows scientists to annotate the regulatory activity in the gene networks previously described. This will help scientists understand how large groups of transcription factors regulate their target genes during drought stress and variable nutrient availability. (Credit: Niklas Frederik Christopher Hummel/Berkeley Lab)

They then carried out an extensive literature review to try to match the function of the transcription factors they had identified en masse with work done previously identifying the function of individual transcription factors in their network.

We were able to show that this is what people saw when they studied the role of transcription factors in gene expression individually, and this is what we saw when we studied them in parallel, Shih said. It actually ended up lining up really well. This makes us confident that we can integrate our data set into gene regulatory networks to identify key transcription factors for engineering important plant traits.

A surprising aspect of the study was the discovery of similar mechanisms of transcriptional regulation between distantly related eukaryotes. By examining the function of transcription factor regulation in both plants and yeast, the researchers uncovered a shared functionality, highlighting the presence of deeply conserved gene regulatory mechanisms.

We were surprised to see that many transcription factor regulatory domains functioned the same way between plants and yeasts, Hummel said. We then expanded on this to demonstrate how machine learning algorithms trained on yeast datasets could work to identify regulatory domains in plants.

The study findings have important implications for agriculture and sustainability. Transcription factors play a crucial role in determining important traits in plants, so understanding how they work will help scientists develop strategies to improve agricultural practices and address environmental challenges.

“We can identify new strategies for designing more drought-tolerant bioenergy crops and other plants with improved agronomic traits.

Niklas Hummel

Looking to the future, the researchers aim to expand their approach to study all transcription factors in Arabidopsis, a widely studied model plant species. This will further accelerate understanding of plant-specific gene regulation and facilitate advances in plant biology.

Our ability to design and modify plants depends on our basic understanding of how various traits are regulated, Shih said. By understanding how key transcription factors may be master regulators of traits of interest, we could identify novel strategies to enhance bioenergy-relevant traits.

This work was supported by the Department of Energy’s Office of Science. JBEI is a bioenergy research center of the DOE.

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Founded in 1931 on the belief that the greatest scientific challenges are best tackled by teams, Lawrence Berkeley National Laboratory and its scientists have received 16 Nobel Prizes. Today, Berkeley Lab researchers develop sustainable energy and environmental solutions, create useful new materials, advance the frontiers of computing, and probe the mysteries of life, matter, and the universe. Scientists around the world rely on laboratory facilities for their scientific discoveries. The Berkeley Lab is a multiprogram national laboratory operated by the University of California on behalf of the US Department of Energy’s Office of Science.

The DOE’s Office of Science is the single largest supporter of basic research in the physical sciences in the United States and is working to address some of the most pressing challenges of our time. For more information, visit energy.gov/science.

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Image Source : newscenter.lbl.gov

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