A paper co-authored by a professor at The University of Texas at Dallas and published recently in the online journal PLoSONE provides details about a fundamental mechanism that governs gene expression in bacteria.

The process of DNA looping, in which two specific DNA sequences located on the same DNA molecule bind simultaneously to a single protein, has also been implicated in the regulation of human genes and in other important processes such as repair of DNA damage.  A key finding in the paper is that in addition to being aided by a bacterial protein known as HU, this process also requires flexibility in the protein that mediates the DNA loop. This inherent flexibility of regulatory proteins and other DNA-binding proteins has not been implicated in the general process of gene regulation until now.

Understanding the basic mechanism of gene regulation is important for characterizing, understanding and ultimately treating diseases, such as Sickle Cell Anemia, among others.

In the paper, titled “Analysis of in-vivo LacR-mediated Gene Repression Based on the Mechanics of DNA Looping,” Dr. Stephen Levene and his colleagues studied the simplest and best-characterized gene-regulatory system, the lac system in E. coli, to determine how DNA looping is involved in repressing key genes involved in bacterial lactose metabolism.  Though HU alone is not enough to promote DNA looping, the researchers found that the protein assembly responsible for repressing the E. coli lac genes is inherently flexible.  This result is likely to be general and apply to proteins called transcription factors that form similar loops in human gene-regulatory systems.

“We know that changes in the levels of transcription factors can dramatically affect the metabolic state of cells and the health of an organism,” Levene said. “These findings underscore the importance of both protein conformation and elasticity in the formation of small DNA loops and demonstrate the importance of analyzing gene regulation in terms of the structure and dynamics of regulatory protein-DNA complexes.”

Levene is an associate professor of molecular and cell biology at UT Dallas. Other authors of the paper are Dr. Yongli Zhang of the Albert Einstein College of Medicine, Abbye McEwen, a former graduate student in UT Dallas’ biotechnology program, and Dr. Donald Crothers of Yale University.

PLoSONE is a publication of the Public Library of Science.

About UT Dallas

The University of Texas at Dallas, located at the convergence of Richardson, Plano and Dallas in the heart of the complex of major multinational technology corporations known as the Telecom Corridor, enrolls more than 14,500 students.  The school’s freshman class traditionally stands at the forefront of Texas state universities in terms of average SAT scores.  The university offers a broad assortment of bachelor’s, master’s and doctoral degree programs.  For additional information about UT Dallas, please visit the university’s Web site at www.utdallas.edu.

Contact Jenni Huffenberger, UT Dallas, (972) 883-4431, jennib@utdallas.edu