July 31, 2020 (Huntsville, Ala.) – Although the Human Genome Project sequenced a nearly-complete human genome almost 20 years ago, only about two percent of the genes in the human genome have been extensively studied and identified as protein-coding genes. Proteins form the basis of living tissues and play a central role in biological processes.
Through a decades long, worldwide collaborative effort with the Encyclopedia of DNA Elements (ENCODE) Project, researchers at HudsonAlpha Institute for Biotechnology, along with collaborators at other institutions, have been trying to elucidate the importance of the remaining 98 percent of the genome. The goal of the Project is to understand how the human genome functions, and to identify the important parts of the human genome.
ENCODE Project’s third phase offers new insights into the organization and regulation of our genes and genome
Results from the latest phase of the project (ENCODE 3) include multiple contributions from the Myers lab at HudsonAlpha, and the laboratories of Barbara Wold, PhD (CalTech); Ross Hardison, PhD (Penn State); Ali Mortazavi, PhD (UC Irvine); and Eric Mendenhall, PhD (University of Alabama in Huntsville and HudsonAlpha); and were published on July 30 as a 9-manuscript compendium in Nature, accompanied by 21 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 detailed press release describing the flagship Nature paper can be found on both the NHGRI and Nature websites.
During the third phase, ENCODE consortium researchers drew closer to their goal of developing a comprehensive map of the functional elements of human and mouse genomes by adding to the ENCODE database millions of candidate DNA switches that regulate when and where genes are turned on. ENCODE 3 also offers a new registry that assigns some of the DNA switches to useful biological categories.
HudsonAlpha researchers perform the largest study of transcription factors expressed at physiological levels to date
As a part of their contribution to ENCODE 3, project manager Mark Mackiewicz, PhD, oversaw HudsonAlpha’s Myers and Mendenhall labs in a study of transcription factor biology in genome-wide experiments to expand the knowledge of DNA elements in both human and mouse genomes. Transcription factors are the largest class of proteins in the human genome and are involved in making an RNA copy of the genes encoded in DNA, which are then used to make proteins that are so important in cells.
All of our cells (barring a few small exceptions) have the same two full copies of our genome. However, in order for the more than 200 different cell types in our body to perform different functions, not all of the genes can be active (or expressed) in every cell type. Gene expression is regulated by the binding of transcription factor proteins to short stretches of DNA, referred to as regulatory elements, that serve as on/off switches for gene expression. The ability of genes to be turned on and off allows for unique combinations of genes to be expressed in each different cell type.
The HudsonAlpha researchers, along with collaborators Mendenhall, Wold, Mortazavi and Hardison, studied about a quarter of all of the expressed transcription factors in a human liver cancer cell line, making it the largest study of transcription factors expressed at physiological, or normal, levels to date.
“Understanding the genomic targets of transcription factors is vitally important to understand many aspects of biology, including gene regulation, development, and to help identify the biological mechanisms of many diseases and disorders,” said Chris Partridge, PhD, senior scientist at HudsonAlpha and co-first author with PhD student Surya Chhetri on the study.
By analyzing such a large group of transcription factors, the researchers were able to identify novel associations between transcription factors, elaborate on their spatial interactions on DNA, and distinguish between those that interact with promoters and those that interact with enhancers in the genome. All of these findings bring researchers one step closer to understanding how the human genome functions, both in normal biology and disease states.
ENCODE Project highlights the importance of collaborative research, a hallmark of HudsonAlpha’s mission
In addition to the ambitious efforts to understand the human genome, a key hallmark of the Project is the complete and rapid open access availability of data generated by members of the ENCODE Consortium which has led to more than 2,000 publications from non-ENCODE researchers who used data generated by the ENCODE Project. Rick Myers, PhD, President, Science Director, and M. A. Loya Chair in Genomics at HudsonAlpha, whose lab has been a member of the ENCODE Consortium since its inception in 2003, says that he is proud of the long-term and wide-reaching collaborative nature of the Project.
“One thing we learned working on the Human Genome Project is that huge endeavors like the ENCODE Project work much more efficiently when research groups coordinate their efforts, particularly because ENCODE’s charge is to generate a resource of data, materials and results that are meant to be used by the entire research and biomedical community,” said Myers. “Another thing we recognized early on is that making the data freely available to everyone on a weekly basis, prior to publication and with no strings attached, allows researchers everywhere to make advances in their research much faster than would otherwise be possible.”
To learn more about the ENCODE Project, you can listen to Myers talk about ENCODE3 and the history of the project on a podcast released by Nature.
About HudsonAlpha: HudsonAlpha Institute for Biotechnology is a nonprofit institute dedicated to developing and applying scientific advances to health, agriculture, learning, and commercialization. Opened in 2008, HudsonAlpha’s vision is to leverage the synergy between discovery, education, medicine, and economic development in genomic sciences to improve the human condition around the globe. The HudsonAlpha biotechnology campus consists of 152 acres nestled within Cummings Research Park, the nation’s second largest research park. The state-of-the-art facilities co-locate nonprofit scientific researchers with entrepreneurs and educators. HudsonAlpha has become a national and international leader in genetics and genomics research and biotech education and fosters more than 40 diverse biotech companies on campus. To learn more about HudsonAlpha, visit hudsonalpha.org.
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