A pre-initiation complex at the 3'-end of genes drives antisense transcription independent of divergent sense transcription

• Published in: Nucleic acids research Vol. 40; no. 6; pp. 2432 - 2444
• Main Authors: Murray, Struan C, Serra Barros, Ana, Brown, David A, Dudek, Peter, Ayling, Jonathan, Mellor, Jane
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.03.2012
• Subjects: 3' Flanking Region; 5' Flanking Region; Antisense; Galactokinase - genetics; Gene Expression Regulation, Fungal; Gene regulation; Gene Regulation, Chromatin and Epigenetics; Promoter Regions, Genetic; Promoters; RNA, Antisense - biosynthesis; RNA, Antisense - genetics; Saccharomyces cerevisiae; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; TATA-Box Binding Protein - metabolism; Terminator Regions, Genetic; Trans-Activators - genetics; Transcription; Transcription Factor TFIIB - metabolism; Transcription, Genetic
• ISSN: 0305-1048; 1362-4962
• DOI: 10.1093/nar/gkr1121

The precise nature of antisense transcripts in eukaryotes such as Saccharomyces cerevisiae remains elusive. Here we show that the 3' regions of genes possess a promoter architecture, including a pre-initiation complex (PIC), which mirrors that at the 5' region and which is much more pronounced at genes with a defined antisense transcript. Remarkably, for genes with an antisense transcript, average levels of PIC components at the 3' region are ∼60% of those at the 5' region. Moreover, at these genes, average levels of nascent antisense transcription are ∼45% of sense transcription. We find that this 3' promoter architecture persists for highly transcribed antisense transcripts where there are only low levels of transcription in the divergent sense direction, suggesting that the 3' regions of genes can drive antisense transcription independent of divergent sense transcription. To validate this, we insert short 3' regions into the middle of other genes and find that they are capable of both initiating antisense transcripts and terminating sense transcripts. Our results suggest that antisense transcription can be regulated independently of divergent sense transcription in a PIC-dependent manner and we propose that regulated production of antisense transcripts represents a fundamental and widespread component of gene regulation.