Transcribe this way: Rap1 confers promoter directionality by repressing divergent transcription

Abstract

In eukaryotes, divergent transcription is a major source of noncoding RNAs. Recent studies have uncovered that in yeast, the transcription factor Rap1 restricts transcription in the divergent direction and thereby controls promoter directionality. Here, we summarize these findings, propose regulatory principles, and discuss the implications for eukaryotic gene regulation.

Keywords: Rap1; directionality; divergent; noncoding RNA; promoter; repression; steric hindrance; transcription factor; yeast.

Figure 1.

Schematic diagram of a bidirectional gene promoter. A bidirectional gene promoter comprises separate core promoters (blue boxes) for the coding messenger RNA (mRNA) and divergent RNA, arranged in opposite orientations. These core promoters are typically located at the edges of a nucleosome-depleted region, flanked by the +1 and −1 nucleosomes (gray circles). The relative amount of transcription from each core promoter dictates the overall “directionality” of the gene promoter. The scale bar illustrates that the output of eukaryotic gene promoters ranges widely: some promoters are more unidirectional, whereas others display more bidirectional transcription.

Figure 2.

Requirements for steric hindrance of divergent transcription initiation. (a) Transcription factor binding site (red boxes) must be within ~50 bp of divergent transcription start site (TSS) for effective repression of transcription. Repression at proximal binding sites does not depend on specific Rap1 motif orientation. (b) Rap1 binding at distal sites, upstream or downstream of the divergent TSS, does not effectively limit the expression of divergent transcripts.