Head-to-head antisense transcription and R-loop formation promotes transcriptional activation

Significance The molecular mechanisms used by noncoding RNAs to regulate gene expression are largely unknown. We have discovered a previously unidentified regulatory phenomenon underlying the transcriptional activation of the intermediate filament protein vimentin. This regulation involves the participation of a previously uncharacterized head-to-head antisense transcript that forms part of a hybrid DNA:RNA structure known as the R loop. R loops have been the focus of recent research regarding their unexpected involvement in gene expression regulation. Antisense-mediated formation of the R loop supports a local chromatin environment that ensures the optimal binding of vimentin transcriptional activators. In addition, we describe how hypermethylation of the locus in a large panel of colon cancer patients is correlated with antisense silencing and, thereby, compromises its regulatory activity.