Researchers from Mount Sinai School of Medicine have identified a previously unknown mechanism by which cells direct gene expression, the process by which information from a gene is used to direct the physical and behavioral development of individuals. The research, which may help scientists gain insight into how muscle and heart diseases develop, is published in the July 8th issue of Nature.
Using a combined approach of structural and molecular biology, a team of researchers led by Ming-Ming Zhou, PhD, Professor and Chair, Structural and Chemical Biology, Mount Sinai School of Medicine, determined that the molecular interactions between proteins are very different than previously thought, and that they play an essential role in the initiation of gene transcription of muscle and the heart. Gene transcription is the first step to gene expression, a cellular process that occurs in response to physiological and environmental stimuli, and is dictated by chemical modifications of the DNA and histones, which are the proteins responsible for packaging the DNA.
Dr. Zhou's team found a new fundamental mechanism in gene transcription through a protein called DPF3b. They learned that DPF3b recognizes gene-activating chemical marks in these histones in a very different way. DPF3b plays a critical role in the copying of genes—a crucial part of the transcription process—for muscle growth and heart development.
"This discovery opens new doors in genome biology research, and has broad implications in the field of epigenetics of human biology of health and disease," said Martin Walsh, PhD, Associate Professor, Pediatrics, and Structural and Chemical Biology at Mount Sinai who is also a co-author of the study. "Knowing that there is an additional way our genome is regulated will allow us to understand the molecular basis of certain human disorders that result from dysregulation of gene expression."
Dr. Zhou said that bromodomains, which are housed in proteins, read off cell signals that turn on genes that determine genetic makeup. "This study uncovers that nature has an alternative to bromodomains for gene expression to initiate, providing a new mechanism to help us understand how our muscles and heart grow properly, and what might cause them to grow abnormally," Dr. Zhou said.
About The Mount Sinai Medical Center
The Mount Sinai Medical Center encompasses both The Mount Sinai Hospital and Mount Sinai School of Medicine. Established in 1968, Mount Sinai School of Medicine is one of few medical schools embedded in a hospital in the United States. It has more than 3,400 faculty in 32 departments and 15 institutes, and ranks among the top 20 medical schools both in National Institute of Health funding and by U.S. News & World Report. The school received the 2009 Spencer Foreman Award for Outstanding Community Service from the Association of American Medical Colleges.
The Mount Sinai Hospital, founded in 1852, is a 1,171-bed tertiary- and quaternary-care teaching facility and one of the nation's oldest, largest and most-respected voluntary hospitals. In 2009, U.S. News & World Report ranked The Mount Sinai Hospital among the nation's top 20 hospitals based on reputation, patient safety, and other patient-care factors. Nearly 60,000 people were treated at Mount Sinai as inpatients last year, and approximately 530,000 outpatient visits took place.
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Journal
Nature