Fine chromatin-driven mechanism of transcription interference by antisense noncoding transcription

Eukaryotic genomes are almost entirely scanned by RNA polymerase II (RNAPII). Consequently, the transcription of long noncoding RNAs (lncRNAs) often overlaps with coding gene promoters triggering potential gene repression through a poorly characterized mechanism of transcription interference. In this study, we propose a global model of chromatin-based transcription interference in Saccharomyces cerevisiae (S. cerevisiae). By using a noncoding transcription inducible strain, we analyzed the relationship between antisense elongation and coding sense repression, nucleosome occupancy and transcription-associated histone modifications using near-base pair resolution techniques. We show that antisense noncoding transcription leads to -1/+1 nucleosome deacetylation via H3K36 trimethylation (H3K36me3). This results in the loss of -1/+1 nucleosome interaction with the RSC chromatin remodeler and subsequent sliding into the Nucleosome-Depleted Region (NDR) hindering Pre-Initiation Complex (PIC) binding. Finally, we extend our model by showing that natural antisense noncoding transcription significantly regulates around 20% of S. cerevisiae genes through this chromatin-based transcription interference mechanism. RNA-seq, MNase-seq, MNase-ChIP-seq, ATAC-seq and ChEC-seq in a Nrd1-AA and Nrd1-AA drpd3 strains treated or not with Rapamycin for 1 hour.