WIKIMEDIA, STEPHEN COLEBOURNE
Bends in the genome called i-motifs, which look like a “W” folded in the middle along the Y axis, lead to the upregulation of a gene, while hairpins in the same location of a gene cause suppression, researchers reported recently at the American Chemical Society meeting in Dallas, Texas. “It’s the sort of evidence we’ve been waiting for” to help confirm the role of i-motifs, John Brazier of the University of Reading who was not part of the study, told Chemical & Engineering News.
In an associated paper, researchers led by Laurence Hurley at Arizona State University showed that when they stabilized the i-motif of the promoter region in a gene called BLC2, protein expression went up. When they maintained this same region of the gene in a hairpin formation, protein expression dropped. “For the first time we propose that the i-motif acts as a molecular switch that controls gene expression and that small molecules that target the dynamic equilibrium of the i-motif and the flexible hairpin can differentially modulate gene expression,” the authors wrote in their study, published last month (February 21) in the Journal of the American Chemical Society.
The findings have practical implications. BLC2 is over-expressed in cancer cells; trapping the gene’s promoter in the hairpin shape using a small molecule made cancer cells more susceptible to chemotherapy.
Edwin Lewis of Mississippi State University who was not involved in the research told Chemical & Engineering News that the results tell “us something we didn’t know before about the regulation of gene expression.”