But he adds, it has been a mystery as to how this chromatin structure is so precisely targeted by specific enzymes and not others.
"By utilizing a technology known as RIP-Chip we were able to examine RNA-protein interaction on a large scale and determine which lincRNAs are associated with each enzyme we examined," he adds. To analyze this tremendous amount of data, coauthor Mitchell Guttman, PhD, a bioinformatician at BIDMC and the Broad Institute, used a mathematical algorithm that identified which lincRNAs are bound by chromatin-modifying enzymes and which are not.
"This analysis revealed that 20 to 30 percent of lincRNAs are bound by three distinct chromatin-modifying complexes," adds Khalil. "By depleting several of these lincRNAs from cells, we were able to show a significant overlap between the genes which become affected by the depletion of lincRNAs and the depletion of the enzymes. This provided us with the evidence that these proteins work together with lincRNAs to target specific regions of the genome."
Standard "textbook" genes encode RNAs that are translated into proteins, and mammalian genomes contain about 20,000 such protein-coding genes. Some genes, however, encode functional RNAs that are never translated into proteins. These include a handful of classical examples known for decades and some recently discovered classes of tiny RNAs, such as microRNAs. By contrast, lincRNAs are thousands of bases long. Because only about 10 examples of functional RNAs were previously identified, they seemed more like genomic oddities than key players. With these latest findings, which also uncovered an additional 1,500 lin
|Contact: Bonnie Prescott|
Beth Israel Deaconess Medical Center