Enhancer RNA Facilitates NELF Release from Immediate Early Genes

Schaukowitch, Katie; Joo, Jae‐Yeol; Liu, Xihui; Watts, Jonathan K.; Martinez, Carlos; Kim, Tae Kyung

doi:10.1016/j.molcel.2014.08.023

Cited by 369 publications

(429 citation statements)

References 51 publications

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“…All these data suggest that in the majority of cases, such unwanted transcripts do not act in cis to regulate gene expression. In case of enhancer RNAs, for which we also did not observe a strong effect on neighboring gene expression, it is possible that transcription itself, rather than the resulting RNA products, has an impact on gene activation; but due to the relatively low number of enhancer RNA analyzed in this study, we cannot exclude that in specific cases such RNAs play a regulatory role, as was suggested previously (Melo et al 2013;Schaukowitch et al 2014).…”

Section: Wwwgenomeorgmentioning

confidence: 50%

DIS3 shapes the RNA polymerase II transcriptome in humans by degrading a variety of unwanted transcripts

et al. 2015

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Human DIS3, the nuclear catalytic subunit of the exosome complex, contains exonucleolytic and endonucleolytic active domains. To identify DIS3 targets genome-wide, we combined comprehensive transcriptomic analyses of engineered HEK293 cells that expressed mutant DIS3, with Photoactivatable Ribonucleoside-Enhanced Cross-Linking and Immunoprecipitation (PAR-CLIP) experiments. In cells expressing DIS3 with both catalytic sites mutated, RNAs originating from unannotated genomic regions increased ∼2.5-fold, covering ∼70% of the genome and allowing for thousands of novel transcripts to be discovered. Previously described pervasive transcription products, such as Promoter Upstream Transcripts (PROMPTs), accumulated robustly upon DIS3 dysfunction, representing a significant fraction of PAR-CLIP reads. We have also detected relatively long putative premature RNA polymerase II termination products of protein-coding genes whose levels in DIS3 mutant cells can exceed the mature mRNAs, indicating that production of such truncated RNA is a common phenomenon. In addition, we found DIS3 to be involved in controlling the formation of paraspeckles, nuclear bodies that are organized around NEAT1 lncRNA, whose short form was overexpressed in cells with mutated DIS3. Moreover, the DIS3 mutations resulted in misregulation of expression of ∼50% of transcribed protein-coding genes, probably as a secondary effect of accumulation of various noncoding RNA species. Finally, cells expressing mutant DIS3 accumulated snoRNA precursors, which correlated with a strong PAR-CLIP signal, indicating that DIS3 is the main snoRNA-processing enzyme. EXOSC10 (RRP6) instead controls the levels of the mature snoRNAs. Overall, we show that DIS3 has a major nucleoplasmic function in shaping the human RNA polymerase II transcriptome.

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Section: Wwwgenomeorgmentioning

confidence: 50%

DIS3 shapes the RNA polymerase II transcriptome in humans by degrading a variety of unwanted transcripts

et al. 2015

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“…Sequences that co-encode both promoter and enhancer activities are the rule rather than the exception, suggesting that enhancer activity shares with promoter activity a common underlying mechanism. One possibility is that enhancer function requires eRNA synthesis (Ørom et al 2010;Kaikkonen et al 2013;Li et al 2013;Mousavi et al 2013;Hsieh et al 2014;Schaukowitch et al 2014). Consistent with this idea, eRNA synthesis at distal enhancers is correlated with transcription of nearby genes (De Santa et al 2010;Kim et al 2010;Rada-Iglesias et al 2010;Arner et al 2015).…”

Section: Discussionmentioning

confidence: 80%

High-throughput functional comparison of promoter and enhancer activities

et al. 2016

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Promoters initiate RNA synthesis, and enhancers stimulate promoter activity. Whether promoter and enhancer activities are encoded distinctly in DNA sequences is unknown. We measured the enhancer and promoter activities of thousands of DNA fragments transduced into mouse neurons. We focused on genomic loci bound by the neuronal activity-regulated coactivator CREBBP, and we measured enhancer and promoter activities both before and after neuronal activation. We find that the same sequences typically encode both enhancer and promoter activities. However, gene promoters generate more promoter activity than distal enhancers, despite generating similar enhancer activity. Surprisingly, the greater promoter activity of gene promoters is not due to conventional core promoter elements or splicing signals. Instead, we find that particular transcription factor binding motifs are intrinsically biased toward the generation of promoter activity, whereas others are not. Although the specific biases we observe may be dependent on experimental or cellular context, our results suggest that gene promoters are distinguished from distal enhancers by specific complements of transcriptional activators.

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“…Plants lack enhancer RNAs (eRNAs) but notably also the NEGATIVE ELONGATION FACTOR (NELF) involved in promoter-proximal pausing (45). eRNAs were reported to mediate release of NELF-dependent pausing (46). Therefore, given the absence of NELF, potential eRNAs may not have provided the same selective advantages in plants.…”

Section: Discussionmentioning

confidence: 99%

Nascent RNA sequencing reveals distinct features in plant transcription

Hetzel

Duttke

Benner

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

148

181

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Transcriptional regulation of gene expression is a major mechanism used by plants to confer phenotypic plasticity, and yet compared with other eukaryotes or bacteria, little is known about the design principles. We generated an extensive catalog of nascent and steadystate transcripts in Arabidopsis thaliana seedlings using global nuclear run-on sequencing (GRO-seq), 5′GRO-seq, and RNA-seq and reanalyzed published maize data to capture characteristics of plant transcription. De novo annotation of nascent transcripts accurately mapped start sites and unstable transcripts. Examining the promoters of coding and noncoding transcripts identified comparable chromatin signatures, a conserved "TGT" core promoter motif and unreported transcription factor-binding sites. Mapping of engaged RNA polymerases showed a lack of enhancer RNAs, promoter-proximal pausing, and divergent transcription in Arabidopsis seedlings and maize, which are commonly present in yeast and humans. In contrast, Arabidopsis and maize genes accumulate RNA polymerases in proximity of the polyadenylation site, a trend that coincided with longer genes and CpG hypomethylation. Lack of promoter-proximal pausing and a higher correlation of nascent and steady-state transcripts indicate Arabidopsis may regulate transcription predominantly at the level of initiation. Our findings provide insight into plant transcription and eukaryotic gene expression as a whole.plant transcription | nascent transcripts | RNA polymerase pausing | 5′GRO-seq | GRO-seq G ene expression is a hallmark of life and subject to adaptation in changing environments. Steady-state transcript levels are a result of transcription initiation, elongation, and termination, followed by maturation and decay. Much has been learned about transcriptional mechanisms using yeast and animal models. In contrast, owing to technical difficulties created by plant cell extracts, there remains a large gap in knowledge in plant transcription. Plants and animals diverged more than 1.6 billion years ago. Studying plant transcription therefore not only contributes to a better understanding of the world's largest food source but also the evolution of eukaryotic gene expression.The signals initiating transcription are ultimately integrated at the promoter. Sequence-specific transcription factors (TFs) commonly bind the proximal promoter around −150 to −50 bp upstream of the transcriptional start site (TSS) (1, 2). At the core promoter, located approximately ±50 bp relative to the TSS, basal TFs cooperate with conserved DNA sequence motifs to orchestrate recruitment of the RNA polymerase (RNAP) (1, 3). Transcription has been studied extensively in a number of species (1-3) but not in plant model systems. Studies focusing on promoterenriched sequences were hindered by the lack of precise TSSs (4, 5) but have improved dramatically through techniques such as paired end analysis of transcription start sites (3PEAT) (6) and cap analysis gene expression (CAGE) (7), but both methods are affected by RNA processing and trans...

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Enhancer RNA Facilitates NELF Release from Immediate Early Genes

Cited by 369 publications

References 51 publications

DIS3 shapes the RNA polymerase II transcriptome in humans by degrading a variety of unwanted transcripts

DIS3 shapes the RNA polymerase II transcriptome in humans by degrading a variety of unwanted transcripts

High-throughput functional comparison of promoter and enhancer activities

Nascent RNA sequencing reveals distinct features in plant transcription

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