Repression of Divergent Noncoding Transcription by a Sequence-Specific Transcription Factor
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ABSTRACT:
PROVIDER: PRJNA432544 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description: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.
| S-EPMC6310685 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2018-12-20 | GSE110004 | GEO
Project description:The directionality of gene promoters, the proportion of protein coding over divergent noncoding transcription, is highly variable and regulated. How promoter directionality is controlled remains poorly understood. We show that chromatin remodelling complex RSC, general regulatory factors (GRFs) including transcription factors (TFs) can facilitate promoter directionality by attenuating divergent noncoding transcription. Depletion of RSC increased divergent noncoding and decreased protein coding transcription of promoters with strong directionality. Consistent with RSC’s role in regulating chromatin, RSC depletion negatively impacts nucleosome positions upstream of the nucleosome depleted region where divergent transcription initiates, suggesting that nucleosome positioning upstream in promoters physically blocks the recruitment of transcription machinery. Likewise, divergent transcription can be suppressed by targeting GRFs and TFs or the bulky dCas9 protein to transcriptional initiation sites. We propose that RSC mediated nucleosome positioning, GRFs including TFs form the physical barriers in promoters for limiting of divergent transcription, thereby controlling promoter directionality.
2021-07-27 | GSE179254 | GEO
Project description:The directionality of gene promoters, the proportion of protein coding over divergent noncoding transcription, is highly variable and regulated. How promoter directionality is controlled remains poorly understood. We show that chromatin remodelling complex RSC, general regulatory factors (GRFs) including transcription factors (TFs) can facilitate promoter directionality by attenuating divergent noncoding transcription. Depletion of RSC increased divergent noncoding and decreased protein coding transcription of promoters with strong directionality. Consistent with RSC’s role in regulating chromatin, RSC depletion negatively impacts nucleosome positions upstream of the nucleosome depleted region where divergent transcription initiates, suggesting that nucleosome positioning upstream in promoters physically blocks the recruitment of transcription machinery. Likewise, divergent transcription can be suppressed by targeting GRFs and TFs or the bulky dCas9 protein to transcriptional initiation sites. We propose that RSC mediated nucleosome positioning, GRFs including TFs form the physical barriers in promoters for limiting of divergent transcription, thereby controlling promoter directionality.
2021-07-27 | GSE179255 | GEO
Project description:Eukaryotic genomes are almost entirely scanned by RNA polymerase II (RNAPII). Consequently, the transcription of long noncoding RNAs (lncRNAs) often overlaps with coding gene promoters triggering potential gene repression through a poorly characterized mechanism of transcription interference. In this study, we propose a global model of chromatin-based transcription interference in Saccharomyces cerevisiae (S. cerevisiae). By using a noncoding transcription inducible strain, we analyzed the relationship between antisense elongation and coding sense repression, nucleosome occupancy and transcription-associated histone modifications using near-base pair resolution techniques. We show that antisense noncoding transcription leads to -1/+1 nucleosome deacetylation via H3K36 trimethylation (H3K36me3). This results in the loss of -1/+1 nucleosome interaction with the RSC chromatin remodeler and subsequent sliding into the Nucleosome-Depleted Region (NDR) hindering Pre-Initiation Complex (PIC) binding. Finally, we extend our model by showing that natural antisense noncoding transcription significantly regulates around 20% of S. cerevisiae genes through this chromatin-based transcription interference mechanism.
2019-05-10 | GSE130946 | GEO
Project description:RSC mediated nucleosome positioning and GRFs form barriers in promoters to limit divergent noncoding transcription
| PRJNA743010 | ENA
Project description: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 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 remodeller. 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 towards productive transcription.
2018-12-20 | GSE107813 | GEO
Project description:We used Native Elongation Transcript sequencing (NET-seq) to investigate the genome-wide effect of the Hda1 histone deacetylase complex (Hda1C) on the repression of divergent non-coding (DNC) transcription at bidirectional promoters in yeast S.cerevisiae.
2021-08-02 | GSE167499 | GEO
Project description:Transcription is typically divergent, initiating at closely spaced oppositely oriented core promoters to produce sense and unstable upstream antisense transcripts (uasTrx). How antisense transcription is regulated and coordinated with sense transcription is largely unknown. Here by combining acute degradation of the multi-functional transcription factor CTCF and nascent transcription measurements, we find that CTCF specifically suppresses antisense but not sense transcription at hundreds of divergent promoters, the great majority of which bear proximal CTCF binding sites. Genome editing, chromatin conformation studies and 5’ transcript mapping revealed that CTCF directly suppresses uasTrx initiation in manner independent of its chromatin architectural function. Primary transcript RNA FISH revealed co-bursting of sense and anti-sense transcripts is disfavored, suggesting CTCF-regulated competition for transcription initiation. In sum, CTCF shapes the noncoding transcriptional landscape by suppressing upstream antisense transcription.
2022-05-02 | GSE173443 | GEO
Project description:Transcription is typically divergent, initiating at closely spaced oppositely oriented core promoters to produce sense and unstable upstream antisense transcripts (uasTrx). How antisense transcription is regulated and coordinated with sense transcription is largely unknown. Here by combining acute degradation of the multi-functional transcription factor CTCF and nascent transcription measurements, we find that CTCF specifically suppresses antisense but not sense transcription at hundreds of divergent promoters, the great majority of which bear proximal CTCF binding sites. Genome editing, chromatin conformation studies and 5’ transcript mapping revealed that CTCF directly suppresses uasTrx initiation in manner independent of its chromatin architectural function. Primary transcript RNA FISH revealed co-bursting of sense and anti-sense transcripts is disfavored, suggesting CTCF-regulated competition for transcription initiation. In sum, CTCF shapes the noncoding transcriptional landscape by suppressing upstream antisense transcription.
2022-05-02 | GSE173442 | GEO