A meta-analysis of microarray datasets has identified a new characteristic of genome regulation. The analysis revealed that microRNAs—derived from genes that do not code for proteins—regulate their chromosomal neighbors. The finding, reported in the March 20 Proceedings of the National Academy of Sciences, adds to the growing evidence that genes located close to each other on the chromosome can be turned on and off together.
Until recently, there was no particular reason to believe that genes in proximity along a chromosome interact with each other. But in the last five years, Isaac Kohane, the Lawrence J. Henderson associate professor of pediatrics and health sciences and technology, and others have discovered that genes near each other often get turned on together. This relationship has been noticed in yeast, worms, and humans.
Kohane and his research team wondered how these genes could be interacting to alter each other’s expression. The researchers turned to microRNAs, which have been shown to increase or degrade a protein without actually coding for protein. MicroRNAs are important during development, and their dysregulation is related to disease phenotypes like cancer. “We wondered whether microRNA could be the cause of a concerted action of genes near each other,” said Kohane, who is also director of the Countway Library of Medicine.
The researchers examined dozens of microarray datasets from mouse tissues looking for patterns of expression near genetic regions encoding microRNA. “On average, we found a massive dip of expression around microRNA,” Kohane said. The suppression of gene expression around microRNA was found in a variety of tissues—including kidney, brain, liver, lung, and heart—suggesting that microRNA’s control is genomewide. Transcription factors were the most commonly suppressed genes, implying that the inhibitory effect of microRNA is indirect.
The analysis also revealed that the amount of microRNA suppression differed according to age. In immature tissue, the dip surrounding microRNA was about 100,000 bases long. The dip extended to 1 million bases in mature tissue.
Genes related to chromatin remodeling, a process that goes awry in disease states such as cancer, were particularly well targeted for silencing by microRNA. “The control of inactivation near microRNAs may cause a predisposition to cancer if disturbed,” Kohane said.
