Wednesday, July 29, 2020
The third phase of the ENCODE Project offers new insights into the organization and regulation of our genes and genome.
The Encyclopedia of DNA Elements Project (ENCODE) is a worldwide effort to understand how the human genome functions. Upon completion of its final phase, the ENCODE Project has added millions of candidate DNA “switches” from the human and mouse genomes that appear to regulate when and where genes are turned on, and a new registry which assigns a portion of these DNA switches. for useful biological categories. The project also offers new visualization tools to help use large ENCODE datasets.
The latest project results have been published in Nature, accompanied by 13 additional in-depth studies published in other major journals. ENCODE is funded by the National Human Genome Research Institute, part of the National Institutes of Health.
“A key priority of ENCODE 3 has been to develop means to share data from thousands of ENCODE experiments with the wider research community to help broaden our knowledge of genome function,” said the NHGRI Director Eric Green, MD, Ph.D. “The ENCODE 3 search and visualization tools make this data accessible, thus advancing open science efforts.”
To evaluate the potential functions of different regions of DNA, ENCODE researchers studied biochemical processes that are typically associated with switches that regulate genes. This biochemical approach is an efficient way to explore the entire genome quickly and comprehensively. This method helps to find regions in DNA that are “candidate functional elements” – regions in DNA that are predicted to be functional elements based on these biochemical properties. Candidates can then be tested in further experiments to identify and characterize their functional roles in gene regulation.
“A major challenge at ENCODE is that different genes and functional regions are active in different cell types,” said Elise Feingold, Ph.D., scientific advisor for strategic implementation in the Division of Genome Sciences at NHGRI and leadership on ENCODE for the institute “This means we need to test a large and diverse number of biological samples to work towards a catalog of candidate functional elements in the genome.”
Significant progress has been made in the characterization of protein-encoding genes, which comprise less than 2% of the human genome. Researchers know much less about the remaining 98% of the genome, including how much and what parts of it perform other functions. ENCODE is helping to fill this significant knowledge gap.
The human body is made up of trillions of cells, with thousands of cell types. While all of these cells share a common set of DNA instructions, the various cell types (e.g., heart, lung, and brain) perform distinct functions using DNA-encoded information differently. . The regions of DNA that act as switches to turn on or off genes, or to afford the exact levels of gene activity, help drive the formation of distinct cell types in the body and regulate their functioning in health and disease.
During the recently completed third phase of ENCODE, researchers performed nearly 6,000 experiments – 4-834 in humans and 1,158 in mice – to shed light on the details of their genes and potential regulators in the ENCODE. their respective genomes.
ENCODE 3 researchers studied the development of mouse embryonic tissues to understand the timeline of various genomic and biochemical changes that occur during mouse development. Mice, because of their genomic and biological similarities to humans, can help inform our understanding of human biology and disease.
These experiments in humans and mice were performed in various biological contexts. Researchers analyzed how chemical modifications of DNA, DNA-binding proteins, and RNA (sister molecule to DNA) interact to regulate genes. Results from ENCODE 3 also help explain how variations in DNA sequences outside protein-encoding regions can influence gene expression, even genes that are distant from a specific variant itself.
“The data generated in ENCODE 3 dramatically increases our knowledge of the human genome, ”said Brenton Graveley, Ph.D., professor and chair of the Department of Genetics and Genome Sciences at UCONN Health. ” The project added enormous resolution and clarity to previous data types, such as DNA-binding proteins and chromatin markers, and new data types, such as long-range DNA interactions and protein-RNA interactions. “
As a new feature, ENCODE 3 researchers have created a resource that details different types of DNA regions and their corresponding candidate functions. A web-based tool called SCREEN allows users to view the data that supports these interpretations.
The ENCODE Project began in 2003 and is an extensive collaborative research effort involving groups across the United States and internationally, consisting of 500 scientists with diverse experience. It has benefited from and built up decades of research on gene regulation conducted by independent researchers around the world. ENCODE researchers have created a community resource, ensuring that project data is accessible to any researcher for their studies. These open science efforts have resulted in more than 2,000 publications by non-ENCODE researchers using the data generated by the ENCODE Project.
“This shows that the encyclopedia is widely used, which is what we have always aimed for,” Dr. Feingold said. “Many of these publications are related to human disease, which testifies to the value of the resource for linking basic biological knowledge to health research.”
NHGRI is one of the 27 institutes and centers in the National Institutes of Health. NHGRI’s Extramural Research Program supports grants for research, and training and career development at sites nationwide. Additional information on NHGRI can be found at https://www.genome.gov.
About the National Institutes of Health (NIH):
NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency that conducts and supports basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.
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