Sense and antisense transcription are associated with distinct chromatin architectures across genes

Abstract

Genes from yeast to mammals are frequently subject to non-coding transcription of their antisense strand; however the genome-wide role for antisense transcription remains elusive. As transcription influences chromatin structure, we took a genome-wide approach to assess which chromatin features are associated with nascent antisense transcription, and contrast these with features associated with nascent sense transcription. We describe a distinct chromatin architecture at the promoter and gene body specifically associated with antisense transcription, marked by reduced H2B ubiquitination, H3K36 and H3K79 trimethylation and increased levels of H3 acetylation, chromatin remodelling enzymes, histone chaperones and histone turnover. The difference in sense transcription between genes with high or low levels of antisense transcription is slight; thus the antisense transcription-associated chromatin state is not simply analogous to a repressed state. Using mutants in which the level of antisense transcription is reduced at GAL1, or altered genome-wide, we show that non-coding transcription is associated with high H3 acetylation and H3 levels across the gene, while reducing H3K36me3. Set1 is required for these antisense transcription-associated chromatin changes in the gene body. We propose that nascent antisense and sense transcription have fundamentally distinct relationships with chromatin, and that both should be considered canonical features of eukaryotic genes.

Native elongating transcript sequencing reveals global anti-correlation between sense and antisense nascent transcription in fission yeast

“…S5C,D). This is consistent with recent observations showing that H3 acetylation is high along genes with antisense transcription in S. cerevisiae (Murray et al 2015).…”

Using both strands: The fundamental nature of antisense transcription

“…Furthermore, mathematical models of transcriptional interference by Sneppen et al 15 have shown that in order for transcription in one direction to impact transcription in the opposite direction, very high levels of transcription are required, possibly above what is typically observed. In Murray et al 9 we demonstrate that antisense transcription is not correlated with sense transcription genome-wide, either positively or negatively. This lack of correlation remained when considering only subsets of genes with different levels of antisense transcription.…”

“…9 Based on this, and the abundant nature of antisense transcription genome-wide, 4 we propose that antisense transcription should be considered a canonical feature of genes, as opposed to an idiosyncrasy particular to just a subset of genes. Future work should seek to understand the function of the dynamic chromatin established by antisense transcription.…”

“…In our recent publication, 9 we asked how genes in S. cerevisiae differ depending on the amount of antisense transcription they experience, to begin to tease apart what this function might be. Using a combination of genome-wide data, computational analyses and experimental, single-gene studies, we identified a broad array of relationships between antisense transcription and other fundamental gene features.…”

“…Antisense transcription was found to associated with decreased DNase I sensitivity over the sense promoter in mammals, 31 indicative of increased nucleosome occupancy, agreeing with our findings in yeast. 9 There is evidence that antisense transcription in mammals might also be involved in mediating the response of a sense promoter to changing environmental cues. Xu et al 25 found that genes with evidence of antisense transcription displayed greater variation in sense transcription across 5 different human cell lines -i.e., that these genes were more transcriptionally plastic.…”