Identification of regulatory elements from nascent transcription using dREG
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ABSTRACT:
PROVIDER: PRJNA501902 | ENA |
REPOSITORIES: ENA
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Project description:Our genomes encode a wealth of transcription initiation regions (TIRs) that can be identified by their distinctive patterns of actively elongating RNA polymerase. We previously introduced dREG to identify TIRs using PRO-seq data. Here, we introduce an efficient new implementation of dREG that uses PRO-seq data to identify both uni- and bidirectionally transcribed TIRs with 70% improvement in accuracy, three- to fourfold higher resolution, and >100-fold increases in computational efficiency. Using a novel strategy to identify TIRs based on their statistical confidence reveals extensive overlap with orthogonal assays, yet also reveals thousands of additional weakly transcribed TIRs that were not identified by H3K27ac ChIP-seq or DNase-seq. Novel TIRs discovered by dREG were often associated with RNA polymerase III initiation, bound by pioneer transcription factors, or located in broad domains marked by repressive chromatin modifications. Our results suggest that transcription initiation can be a powerful tool for expanding the catalog of functional elements.
| S-EPMC6360809 | biostudies-literature
Project description:Nascent RNA variation reveals architecture and interactions of transcribed regulatory elements
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Project description:Our genomes encode a wealth of transcription initiation regions (TIRs) that can be identified by their distinctive patterns of transcription initiation. We previously introduced dREG to identify TIRs using PRO-seq data. Here we introduce an efficient new implementation of dREG that uses PRO-seq data to identify both uni- and bidirectionally transcribed TIRs with 70% improvements in accuracy, 3-4-fold higher resolution, and >100-fold increases in computational efficiency. Using a novel strategy to identify TIRs based on their statistical confidence reveals extensive overlap with orthogonal assays, yet also reveals thousands of additional weakly-transcribed TIRs that were not identified by H3K27ac ChIP-seq or DNase-I-hypersensitivity. Novel TIRs discovered by dREG were often associated with RNA polymerase III initiation or bound by transcription factors that recognize DNA concurrently with a nucleosome. We provide a web interface to dREG that can be used by the scientific community (http://dREG.DNASequence.org).
2018-10-31 | GSE121993 | GEO
Project description:Active transcriptional regulatory elements are bidirectionally transcribed, the level of transcription correlating with regulatory activity. Using capped nascent RNA sequencing (PRO-cap) in 69 human lymphoblastoid cell lines, we identify 87,826 transcribed transcriptional regulatory elements (tTREs) and thousands of genetic variants that associate with tTRE transcription. Many of these variants associate with gene expression and are enriched at specific positions – central transcription factor (TF) binding sites or surrounding transcription start sites – consistent with a dual-hub tTRE architecture. Additionally, co-expression analyses reveal interactions between tTREs. We find evidence of TFs influencing mid- to long-range interactions and of strand-dependent cooperativity at closely-spaced tTREs.
2018-10-16 | GSE110638 | GEO
Project description:Transcription factors (TFs) bind specific sequences in promoter-proximal and distal DNA elements in order to regulate gene transcription. RNA is transcribed from both promoter-proximal and distal DNA elements, and some DNA-binding TFs have also been shown to bind RNA. These obsevations led us to postulate that RNA transcribed from regulatory elements contributes to stable TF occupancy at these regulatory elements. We show here that the ubiquitously expressed TF YY1 binds to both proximal and distal regulatory elements and to the RNA species associated with these elements near active genes in embryonic stem cells. Inhibition of transcription from these elements reduces YY1 occupancy. In contrast, tethering of RNA species near YY1 DNA binding sites enhances YY1 occupancy. We propose that RNA acts as trap to maintain certain TFs at active enhancer and promoter-proximal regulatory elements. Thus, transcriptional control generally involves a positive feedback loop, where YY1 and other TFs stimulate local transcription, and newly transcribed nascent RNA reinforces local TF occupancy. This model helps explain why TFs occupy only the small fraction of their consensus motifs in the mammalian genome where transcription is detected. GRO-Seq in mouse embryonic stem cells treated with transcription-altering drugs
2015-10-29 | E-GEOD-68197 | biostudies-arrayexpress
Project description:Transcription factors (TFs) bind specific sequences in promoter-proximal and distal DNA elements in order to regulate gene transcription. RNA is transcribed from both promoter-proximal and distal DNA elements, and some DNA-binding TFs have also been shown to bind RNA. These obsevations led us to postulate that RNA transcribed from regulatory elements contributes to stable TF occupancy at these regulatory elements. We show here that the ubiquitously expressed TF YY1 binds to both proximal and distal regulatory elements and to the RNA species associated with these elements near active genes in embryonic stem cells. Inhibition of transcription from these elements reduces YY1 occupancy. In contrast, tethering of RNA species near YY1 DNA binding sites enhances YY1 occupancy. We propose that RNA acts as trap to maintain certain TFs at active enhancer and promoter-proximal regulatory elements. Thus, transcriptional control generally involves a positive feedback loop, where YY1 and other TFs stimulate local transcription, and newly transcribed nascent RNA reinforces local TF occupancy. This model helps explain why TFs occupy only the small fraction of their consensus motifs in the mammalian genome where transcription is detected. CLIP-Seq for YY1 in mouse embryonic stem cells
2015-10-29 | E-GEOD-68196 | biostudies-arrayexpress
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Project description:Identification of Functional Regulatory Elements in the Human Genome Using Pooled CRISPR Screens
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Project description:Transcription factors (TFs) bind specific sequences in promoter-proximal and distal DNA elements in order to regulate gene transcription. RNA is transcribed from both promoter-proximal and distal DNA elements, and some DNA-binding TFs have also been shown to bind RNA. These obsevations led us to postulate that RNA transcribed from regulatory elements contributes to stable TF occupancy at these regulatory elements. We show here that the ubiquitously expressed TF YY1 binds to both proximal and distal regulatory elements and to the RNA species associated with these elements near active genes in embryonic stem cells. Inhibition of transcription from these elements reduces YY1 occupancy. In contrast, tethering of RNA species near YY1 DNA binding sites enhances YY1 occupancy. We propose that RNA acts as trap to maintain certain TFs at active enhancer and promoter-proximal regulatory elements. Thus, transcriptional control generally involves a positive feedback loop, where YY1 and other TFs stimulate local transcription, and newly transcribed nascent RNA reinforces local TF occupancy. This model helps explain why TFs occupy only the small fraction of their consensus motifs in the mammalian genome where transcription is detected. Affinity purification (ChIP-Seq) for YY1 in mouse embryonic stem cells treated with transcription-affecting compounds
2015-05-28 | E-GEOD-68195 | biostudies-arrayexpress