The third phase of the ENCODE project offers new ideas for the organization and regulation of our genes and genome.
Encyclopedia of DNA The Elements Project (ENCODE) is a worldwide attempt to understand how the human genome works. With the completion of its final phase, the ENCODE project has added millions of candidate DNA “switches”
The latest project results were published in nature, accompanied by 13 additional in-depth studies published in other major journals. ENCODE is funded by the National Institute for Human Genome Research, part of the National Institutes of Health.
“ENCODE 3’s top priority was to develop tools to share data from thousands of ENCODE experiments with the wider research community to help broaden our understanding of genome function,” said NHGRI Director Eric Green, Ph.D. , Doctor of Science. “ENCODE 3 search and visualization tools make this data available, thus increasing efforts in open science.”
To assess the potential functions of different DNA regions, ENCODE researchers investigated the biochemical processes that are usually associated with the switches that regulate genes. This biochemical approach is an effective way to quickly and comprehensively study the entire genome. This method helps to locate regions in DNA that are “candidate functional elements” – DNA regions that are thought to be functional elements based on these biochemical properties. Candidates can then be tested in additional experiments to identify and characterize their functional roles in gene regulation.
“A key challenge at ENCODE is that different genes and functional regions are active in different cell types,” said Ellis Feingold, Ph.D. “This means that we have to test a large and diverse number of biological samples to work on a catalog of candidate functional elements in the genome.”
Significant progress has been made in characterizing protein-encoding genes that contain less than 2% of the human genome. Researchers know much less about the other 98% of the genome, including how many and which parts of it perform other functions. ENCODE helps 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, different cell types (e.g., heart, lung, and brain) perform different functions using the information encoded in DNA in different ways. DNA regions, which act as switches to turn genes on or off or set the right levels of gene activity, help stimulate the formation of different cell types in the body and control 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 details of genes and their potential regulators in their respective genomes.
ENCODE 3 researchers investigated the development of embryonic mouse tissues to understand the timeline of various genomic and biochemical changes occurring 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 on humans and mice were performed in several biological contexts. The researchers analyzed how the chemical modifications of DNA, the proteins that bind to DNA, and RNA (sister DNA molecule) interact to regulate genes. The results of ENCODE 3 also help explain how variations in DNA sequences outside the regions encoding a protein can affect the expression of genes, even genes located far from the particular variant.
“The data generated in ENCODE 3 dramatically increases our understanding of the human genome, ”said Brenton Graley, PhD and Chair of Genetics and Genomic Sciences at UCONN Health. “The project added tremendous resolution and clarity to previous data types, such as DNA-binding proteins and chromatin markers, as well as new data types, such as long-distance 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 respective candidate functions. A web-based tool called SCREEN allows users to visualize the data supporting these interpretations.
The ENCODE project was launched in 2003 and is a broad collaborative research effort involving groups in the United States and internationally, involving more than 500 scientists with diverse knowledge. He has benefited from and built decades of research into gene regulation by independent researchers around the world. ENCODE researchers have created a community resource by ensuring that project data is available to each researcher for their research. These open science efforts have resulted in more than 2,000 publications by non-ENCODE researchers using data generated by the ENCODE project.
“This shows that the encyclopedia is widely used, this is what we have always strived for,” says Dr. Feingold. “Many of these publications are related to human disease, which testifies to the value of the resource for linking basic biological knowledge with health research.”
Reference: Project Encyclopedia of DNA Elements (ENCODE)