Regulation of transcriptional interference by the Swi/Snf complex [RNA-seq]

Alternative transcription start sites regulate transcript isoform diversity and, in turn, often regulate translation levels for a given gene. Recently, a form of gene regulation was described in which transcriptional and translational interference are coordinated, resulting in transcript isoform-dependent changes in protein expression for affected genes. In this form of gene regulation, a long undecoded transcript isoform (LUTI) is transcribed from a gene-distal promoter, interfering with expression of the gene-proximal promoter. While transcriptional and chromatin features associated with LUTI expression have been described, the mechanism underlying LUTI-based transcriptional interference is not well-understood. Using an unbiased genetic approach followed by integrated genomic analysis, we have found that the Swi/Snf chromatin remodeling complex is required for co-transcriptional nucleosome remodeling that leads to LUTI-mediated repression. We uncovered twelve genes with tandem promoters that rely on Swi/Snf function for transcriptional interference during protein folding stress, including three LUTI-regulated genes. Our results provide evidence that, in addition to its canonical function in gene activation, the Swi/Snf complex directly represses promoters that are subject to transcriptional readthrough. Samples were grown as described in Morse et al. , 2023. Cells were collected in mid-log phase from YPD media. 3 biological replicates are included for each genotype