GSE104712
Effect of HDAC inhibition on nascent transcription by RNAPII in fission yeast
Recent studies have revealed that eukaryotic genomes are pervasively transcribed by RNA polymerase II, producing a plethora of non-coding RNAs which frequently overlap protein-coding genes. Despite the fact that overlapping transcription is well known to repress transcription initiation from downstream promoters, the mechanism behind this phenomenon has remained elusive. It was proposed that transcriptional interference relies on the act of transcription rather than the RNA itself to block access of the transcription machinery to downstream promoters. Here, we use the fission yeast Schizosaccharomyces pombe to demonstrate that an RNA and chromatin-dependent mechanism is responsible for transcriptional interference. This relies on co-transcriptional recruitment of the histone deacetylase Clr3 to nascent non-coding RNA, leading to formation of hypoacetylated chromatin and repression of the downstream protein-coding gene. Our findings highlight the unexpected requirement for RNA as well as trans-acting protein factors in mediating the repressive effects imposed on gene expression through overlapping non-coding transcription. Overall design: NET-seq was performed in WT cells either untreated (-TSA) or treated (+TSA) for 2.5 hours with 20 µg/ml of the HDAC inhibitor Trichostatin A (TSA). Both samples were sequenced in duplicates.