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DALLAS – May 13, 2024 – A team led by researchers at UT Southwestern Medical Center identifies a set of simple rules that control the activity of promoters, the regions of DNA where genes begin the process of producing proteins. We have developed a deep learning model for. Their findings are: sciencecould lead to a better understanding of how promoters contribute to gene regulation in health and disease.
Dr. Jian Zhou is an assistant professor in the Lyda Hill Department of Bioinformatics at UT Southwestern, a Lupe Murchison Foundation Medical Research Scholar, and a member of the Harold C. Simmons Comprehensive Cancer Center.
“Promoters are essential to the function of all genes, but our understanding of how these genetic elements function remains limited, despite decades of research revealing many of their characteristics. incomplete. Our study sheds new light on how these sequences function in humans and other mammals,” said Jian Zhou, Ph.D., an assistant professor in the UT Southwestern Lydda Hill School of Bioinformatics. Stated. Dr. Chou co-led the study with first author Ksenia Dudnik, a graduate student in the Chou lab, and Dr. Jiang Xu, a former research associate at the University of Texas Southwestern Children's Medical Center Research Institute.
The creation of the proteins that cells use to carry out their activities begins with a process known as transcription. During this time, the RNA polymerase protein latches onto the DNA strand and copies it. – or transcribe – The encoded information is incorporated into RNA molecules. The region where RNA polymerase binds and initiates transcription is called the promoter. In humans, promoters are typically made up of hundreds of base pairs, the building blocks of DNA. Researchers have identified common base-pair sequences shared between some regions of DNA that are promoters, but these sequences are often absent in human promoters, and it is unclear how the DNA sequences The rules that direct the transcription process remain unclear.
Kseniia Dudnyk is a graduate student in the Zhou lab at UT Southwestern.
To better define human promoters and how they work, researchers developed a machine learning program they named Puffin. After analyzing data from tens of thousands of recognized human promoters, the program determined that they were composed of three types of sequence patterns: motifs, initiators, and trinucleotides.
Puffins showed that depending on how these elements are arranged, gene transcription can be activated or repressed. Puffin also predicted how the arrangement of these elements would cause her RNA polymerase to preferentially transcribe a single strand of DNA, or both strands simultaneously in opposite directions. can. This bidirectional transcription is common in human genes.
The program also showed that mice and other mammals share a similar set of rules for controlling promoter operation. Additionally, Puffin allows researchers to predict whether and how transcription will occur if they mutate a promoter, and the results are generally consistent with experimental results. Ta.
The study authors say puffin may help us understand how promoters function in healthy cells and how disease-related promoter changes cause changes in gene transcription. suggested. The program is available for free on his web server (tss.zhoulab.io) so other researchers can test promoter sequences of interest. They added that using similar machine learning approaches could provide insight into other aspects of the genome that are still poorly understood.
Other UTSW researchers who contributed to this study are Donghong Cai, Ph.D., a postdoctoral fellow with the Xu lab, and Chenlai Shi, Ph.D., data scientist.
This research was funded by grants from the National Institutes of Health (DP2GM146336, R01DK111430, R01CA230631, and R01CA259581). Cancer Prevention Research Institute of Texas (RR190071); and Leukemia and Lymphoma Society Scholar Award recipient.
Dr. Chou is a Lupe Murchison Foundation Medical Research Fellow and a member of the Harold C. Simmons Comprehensive Cancer Center.
About UT Southwestern Medical Center
UT Southwestern is one of the nation's leading academic medical centers, combining pioneering biomedical research with outstanding clinical care and education. The institution's faculty have won six Nobel Prizes, including 25 members of the National Academy of Sciences, 21 members of the National Academy of Medicine, and 13 Howard Hughes Medical Institute investigators. There is. Our more than 3,100 full-time faculty members are responsible for groundbreaking medical advances and are committed to rapidly translating science-driven research into new clinical treatments. Physicians at the University of Texas Southwestern provide care to more than 120,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5 million outpatient visits annually in more than 80 specialties. I am.
