The Effect of Spt5p on Transcriptional Directionality

SPT5 is a well-conserved factor that manipulates multiple stages of transcription, including promoter-proximal pausing (PPP). Furthermore, recent studies have reported an unidentified increase of antisense transcripts near promoters in SPT5 mutations. Here, we have identified Spt5p-restricted intragenic antisense transcripts that are in close relationship with sense transcription. The antisense highly-restricted genes have two common properties: endogenously strong sense transcription and weak antisense transcription, which is also conserved in humans. We identified that Spt5p depletion reduces H3K36me3 and H3K79me3 and leads to histone hyperacetylation, which might be the intermediate stage to induce antisense transcription. We also found possible termination factors that are involved in the antisense restriction with Spt5p. By unveiling the new role of SPT5 in finely balancing the transcription bidirections, we revealed that transcription machinery can determine the direction cotranscriptionally.