Repression of Divergent Noncoding Transcription by a Sequence-Specific Transcription Factor

序列特异性转录因子对非编码序列差异转录的抑制

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作者:Andrew C K Wu ,Harshil Patel ,Minghao Chia ,Fabien Moretto ,David Frith ,Ambrosius P Snijders ,Folkert J van Werven

Abstract

Many 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. Keywords: RSC; Rap1; directionality; divergent; noncoding RNA; promoter; repression; transcription; transcription factor; yeast.

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