Farmington, Conn.—Probing human genomic data with a variety of computational tools—including some borrowed from social networks—researchers at The Jackson Laboratory and an international team of collaborators discovered that interactions vital to transcriptional regulation are organized in a large-scale, three-dimensional network.
Yijun Ruan, Ph.D.Jackson Laboratory Professor Yijun Ruan, Ph.D., led the research published in the Oct. 25 edition of Cell Reports in collaboration with Jackson President and CEO Edison Liu, M.D., and researchers in Singapore, India, Australia, Croatia and Hungary. Their systems-level conceptual framework—a “chromatin interactome"—offers new insights into complex traits in humans.
In what’s known as the “central dogma” of genetics, RNA duplicates DNA in a process called transcription, creating messenger RNA, which in turn continues the process of building the proteins needed by the cell. These include components of chromatin, the fundamental building material inside the cell nucleus.
Composed of DNA and proteins, chromatin compresses DNA so that it fits inside the nucleus and provides DNA with the structural integrity it needs to undergo replication without damage. Chromatin itself interacts throughout the cell in many ways, and the research team chose to study chromatin interactions associated with RNA polymerase II, an enzyme that catalyzes the transcription process.
The researchers found that 40 percent of the total genomic elements involved in chromatin interactions converged to a giant, hierarchical network organized into chromatin “communities.” And just as some Twitter and Facebook users are more influential than others, so are some of these communities.
“We borrowed concepts and some of the algorithms and other computational tools used in social networks,” Ruan explains, “to view and dissect chromatin interaction networks. In so doing, we were able to visualize how the genome appears to organize genes with related functions into certain communities. We also observed that some genes are in the ‘rich clubs’ with more crucial roles than others.”
If a member of one of these “rich clubs” experienced a mutation or other malfunction, the entire organism could be affected, Ruan notes, as may occur in complex human diseases. “Our study represents a pioneering effort of using complex network tools to reveal new insights into complex human traits, including diseases.”
The Jackson Laboratory is an independent, nonprofit biomedical research institution based in Bar Harbor, Maine, with a facility in Sacramento, Calif., and a new genomic medicine institute in Farmington, Conn. It employs a total staff of more than 1,400. Its mission is to discover the genetic basis for preventing, treating and curing human disease and to enable research and education for the global biomedical community.
Sandhu et al., Large-Scale Functional Organization of Long-Range Chromatin Interaction Networks, Cell Reports (2012)
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