Abstract

SummaryMany active eukaryotic gene promoters exhibit divergent noncoding transcription, but the mechanisms restricting expression of these transcripts are not well understood. Here, we demonstrate how a sequence-specific transcription factor represses divergent noncoding transcription at highly expressed genes in yeast. We find that depletion of the transcription factor Rap1 induces noncoding transcription in a large fraction of Rap1-regulated gene promoters. Specifically, Rap1 prevents transcription initiation at cryptic promoters near its binding sites, which is uncoupled from transcription regulation in the protein-coding direction. We further provide evidence that Rap1 acts independently of previously described chromatin-based mechanisms to repress cryptic or divergent transcription. Finally, we show that divergent transcription in the absence of Rap1 is elicited by the RSC chromatin remodeler. We propose that a sequence-specific transcription factor limits access of basal transcription machinery to regulatory elements and adjacent sequences that act as divergent cryptic promoters, thereby providing directionality toward productive transcription.

Highlights

  • Precise control of gene expression is critical for all cellular functions

  • Transcription of divergent cryptic unstable transcripts (CUTs) and SUTs typically correlates with nucleosome-depleted regions (NDRs) and promoter activity in the coding gene direction

  • The transcript with the strongest signal approximated the size of the adjacent MLP1 gene, which we define as isoform of MLP1

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Summary

Graphical Abstract

Andrew C.K. Wu, Harshil Patel, Minghao Chia, Fabien Moretto, David Frith, Ambrosius P. Wu et al characterize how divergent noncoding RNAs are repressed at highly expressed gene promoters in yeast. The authors identified that the sequencespecific transcription factor Rap restricts transcription initiation in the divergent direction locally near its binding site, thereby controlling promoter directionality. 2018, Molecular Cell 72, 942–954 December 20, 2018 a 2018 The Author(s).

SUMMARY
INTRODUCTION
RESULTS
C FHL1 -AID
80 Wild type
B Chr VII
METHOD DETAILS
Full Text
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