The third phase of the ENCODE project offers new perspectives on the organization and regulation of our genes and genomes.
encyclopedia DNA Elements (ENCODE) The project is a worldwide effort to understand how the human genome works. Following its final phase, the ENCODE project has added millions of candidate DNA “switch”; switches from human and mouse genomes that appear to regulate when and where genes are turned on, and a new registry to assign some of these DNA switches. into useful biological categories. The project also offers new visualization tools to help use large ENCODE datasets.
The latest results of the project were published in 2007 nature, together with 13 other in – depth studies published in other major journals. ENCODE is funded by the National Research Institute for the Human Genome, which is part of the National Institutes of Health.
“The main priority of the ENCODE 3 program 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, MD, Ph.D. “ENCODE 3’s search and visualization tools make this data available, increasing effort in open science.”
To assess the potential functions of different regions of DNA, ENCODE scientists have studied the biochemical processes that are usually associated with gene regulatory switches. This biochemical approach is an effective way to examine the entire genome quickly and comprehensively. This method helps to locate regions of DNA that are “candidate functional elements” – regions of DNA that are thought 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.
“The key challenge at ENCODE is that different genes and functional regions are active in different cell types,” said Elise Feingold, Ph.D., Scientific Adviser for Strategic Implementation at the NHGRI Division of Genome Sciences and leadership at ENCODE for the institute. “This means we need 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 proteins encoding proteins that make up less than 2% of the human genome. Scientists know much less about the remaining 98% of the genome, including how many and which parts perform other functions. ENCODE helps fill this important 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 by differently using the information encoded in the DNA. DNA regions, which act as switches to turn genes on or off or to tune precise levels of gene activity, help control the production of different types of cells in the body and control their functioning in health and disease.
During the recently completed third phase of the ENCODE program, researchers performed nearly 6,000 experiments – 4,844 in humans and 1,158 in mice – to shed light on the details of genes and their potential regulators in their respective genomes.
The researchers of the ENCODE 3 study studied the development of embryonic mouse tissues to understand the timing of the various genomic and biochemical changes that occur during mouse development. Mice can help inform our understanding of human biology and disease through their genomic and biological similarities to humans.
These experiments on humans and mice were performed in several biological contexts. The researchers analyzed both chemical modifications of DNA, proteins that bind to DNA, and RNA (sister DNA molecule) interact to regulate genes. The results from ENCODE 3 also help explain how variations in DNA sequences outside the protein coding regions can affect the expression of genes, even genes located far from the specific variant itself.
“The data generated in ENCODE 3 dramatically enhances our understanding of the human genome, ”said Brenton Graveley, Ph.D., Professor and President of UCONN Health’s Department of Genetics and Genetic Sciences. “The project has added tremendous resolution and clarity to previous data types, such as DNA binding proteins and chromatin tags, 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 detailing the different types of DNA regions and their corresponding candidate functions. A web tool called SCREEN allows users to visualize data that supports these interpretations.
Launched in 2003, the ENCODE project is a large-scale research effort involving groups from the US and abroad, involving more than 500 scientists with a variety of expertise. It has benefited from decades of research on gene regulation by independent researchers around the world. ENCODE researchers have created a community resource and ensured that project data is accessible to any researcher for the purposes of their studies. The result of this open science effort has been more than 2,000 publications from non-ENCODE researchers who have used data generated by the ENCODE project.
“This proves that the encyclopedia is widely used, which we have always strived for,” said Dr. Feingold. “Many of these publications relate to human diseases, which confirms the value of a resource for linking basic biological knowledge to health research.”
Reference: Project Encyclopedia of DNA Elements (ENCODE)