High-resolution map of yeast genome can shed light on development responses in higher organisms

A new study performed by Penn State and Cornell University explains an effort to create the most detailed and high-resolution map of gene regulation and chromosome architecture in yeast organisms, for the first time.

Yeast

Yeast. Image Credit: Fascinadora/Shutterstock.com

The study is a crucial step toward enhancing one’s understanding of evolution, development, environmental responses in higher organisms.

In particular, the analysis mapped the accurate binding sites of over 400 different chromosomal proteins in the yeast genome, the majority of which control gene expression.

Yeast cells offer a basic model system with 6,000 genes, and most of these genes are found in other species, including human beings, rendering them exceptional candidates for analyzing complex biological pathways and fundamental genetics.

The article titled, “The high-resolution protein architecture of the budding yeast genome,” was recently published in the Nature journal.

It's a vastly more complex proposition, but like the sequencing of the yeast genome preceded the sequencing of the human, I'm sure we will be able to see the regulatory architecture of the human genome.”

B. Franklin Pugh, Study Senior Author and Professor of Molecular Biology and Genetics, College of Arts and Sciences

Pugh is also a former professor at Pennsylvania State University, where he started this study. Matthew Rossi is the first author of the article and a research assistant professor at Penn State.

Using a method known as ChIP-exo the researchers mapped the binding sites of around 400 various proteins that communicate with the yeast genome, a few at certain locations and others at an unlimited number of sites.

The researchers conducted over 1,200 separate CHIP-exo tests, creating billions of individual data points. To study this vast amount of data, Penn State’s supercomputing clusters and the development of many new bioinformatic tools were needed to detect patterns and to expose the organization of regulatory proteins in the yeast genome.

The study showed a remarkably small number of distinct protein assemblies used repeatedly across the yeast genome.

The study also demonstrated two different gene regulatory architectures, widening the standard model of gene regulation. The supposed constitutive genes—those that carry out basic “housekeeping” roles and are almost invariably active at low levels—needed just a basic series of regulatory controls, while those triggered by environmental signals, called inducible genes, had a more dedicated architecture.

The conventional model of gene regulation involves proteins, known as transcription factors, which attach to particular DNA sequences to regulate the expression of nearby genes.

But the investigators discovered that “housekeeping: genes”—which make up the majority of genes in yeast—did not contain a protein-DNA architecture that would enable the attachment of particular transcription factors—a hallmark of inducible genes.

The resolution and completeness of the data allowed us to identify 21 protein assemblages and also to identify the absence of specific regulatory control signals at housekeeping genes. The computational methods that we've developed to analyze this data could serve as a jumping-off point for further development for gene regulatory studies in more complex organisms.”

Shaun Mahony, Study Co-Author and Assistant Professor of Biochemistry and Molecular Biology, Penn State

Source:
Journal reference:

Rossi, M. J., et al. (2021) A high-resolution protein architecture of the budding yeast genome. Nature. doi.org/10.1038/s41586-021-03314-8.

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