Mediator is a conserved, essential transcriptional coactivator complex, but its in vivo functions have remained unclear due to conflicting data regarding its genome‐wide binding pattern obtained by genome‐wide ChIP. Here, we used ChEC‐seq, a method orthogonal to ChIP, to generate a high‐resolution map of Mediator binding to the yeast genome. We find that Mediator associates with upstream activating sequences (UASs) rather than the core promoter or gene body under all conditions tested. Mediator occupancy is surprisingly correlated with transcription levels at only a small fraction of genes. Using the same approach to map TFIID, we find that TFIID is associated with both TFIID‐ and SAGA‐dependent genes and that TFIID and Mediator occupancy is cooperative. Our results clarify Mediator recruitment and binding to the genome, showing that Mediator binding to UASs is widespread, partially uncoupled from transcription, and mediated in part by TFIID.
A high‐resolution map of Mediator distribution in the yeast genome shows preferential binding to upstream activating sequences, poor correlation with transcription levels, and a cooperative role for TFIID and Mediator on target genes.
ChEC‐seq provides a ChIP‐independent means by which to map the genomic distribution of Mediator.
Mediator binds to UASs rather than core promoters or gene bodies.
Mediator binding to UASs is broadly uncoupled from transcriptional activity.
TFIID associates with the promoters of both annotated SAGA‐ and TFIID‐dependent genes.
Mediator and TFIID chromatin association is cooperative.
- Received June 15, 2016.
- Revision received August 30, 2016.
- Accepted September 20, 2016.
- © 2016 The Authors