Divergent transcription from active promoters

By A. C. Seila, J. M. Calabrese, S. Levine, Gene W. Yeo, P. Rahl, Ryan A. Flynn, Richard A. Young, Phillip A. Sharp. Science, 2008

913 citations recorded by the source corpus.

Transcription initiation by RNA polymerase II (RNAPII) is thought to occur unidirectionally from most genes. Here, we present evidence of widespread divergent transcription at protein-encoding gene promoters. Transcription start site–associated RNAs (TSSa-RNAs) nonrandomly flank active promoters, with peaks of antisense and sense short RNAs at 250 nucleotides upstream and 50 nucleotides downstream of TSSs, respectively. Northern analysis shows that TSSa-RNAs are subsets of an RNA population 20 to 90 nucleotides in length. Promoter-associated RNAPII and H3K4-trimethylated histones, transcription initiation hallmarks, colocalize at sense and antisense TSSa-RNA positions; however, H3K79-dimethylated histones, characteristic of elongating RNAPII, are only present downstream of TSSs. These results suggest that divergent transcription over short distances is common for active promoters and may help promoter regions maintain a state poised for subsequent regulation.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/840eae6c4f9317de818a772288b94329e3c39270

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Citations in the corpus

Transcription factors interact with RNA to regulate genes (2022, background): “RNA molecules are produced at loci where TFs are bound, but their roles in gene regulation are not wellunderstood (Kaikkonen and Adelman, 2018; Seila et al., 2008).”
Genome-wide characterization of transcriptional start sites in humans by integrative transcriptome analysis. (2011, background): “…(Berretta and Morillon 2009; Jacquier 2009; Neil et al. 2009), ‘‘stable unannotated transcripts (SUTs)’’ (Xu et al. 2009), and other emerging classes of RNAs (Preker et al. 2008; Seila et al. 2008; Affymetrix/ Cold Spring Harbor Laboratory ENCODE Transcriptome Project 2009; Taft et al. 2009).”
Gene regulation by the act of long non-coding RNA transcription (2013, background): “The association of lncRNA transcription with gene activation needs, however, to be considered within the framework that most protein-coding gene promoters in yeast and mammalian cells give rise to a bidirectional antisense lncRNA transcript [106,107].”
RNA sequencing: advances, challenges and opportunities (2010, background): “Subsequently, the use of other NGS platforms with higher throughput has resulted in genome-wide surveys and the discovery of an ever-growing number of sRNA specie”
Histone H3K27ac separates active from poised enhancers and predicts developmental state (2010, background): “We asked whether H3K27ac-enriched enhancers selectively expressed these short RNAs using a small RNA-Seq data set previously published (22) and found that these short RNAs are indeed selectively transcribed from H3K27ac-positive over H3K27ac-negative enhancer elements (Fig.”
Localization and abundance analysis of human lncRNAs at single-cell and single-molecule resolution (2015, methodology): “While almost all divergent transcription results in short unstable transcripts [41-43,72,73], we and others have reported over 500 lincRNAs that are transcribed divergently to protein coding genes [9,35,62].”
The rise of regulatory RNA (2014, background): “There are also other reports of less distinct classes of promoter-associated RNAs called PASRs 125 , TSSa-RNAs 126 and PROMPTS 127 , some of which may play a role in RNA-directed transcriptional gene silencing 128 .”
Non‐coding RNAs: regulators of disease (2010, background): “An explanation for this apparent paradox comes from two unexpected findings: (a) that biological complexity generally correlates with the proportion of the genome that is non-protein-coding [1]; and (b) that, while only 2% of the mammalian genome encodes mRNAs, the vast majority is transcribed, larg”
Mechanisms of Polycomb gene silencing: knowns and unknowns (2009, background): “Genome-wide analyses in mammals show that ∼30% of all genes contain paused RNA polymeras”
Determinants of enhancer and promoter activities of regulatory elements (2019, background): “Core (2008), Seila (2008) and Preker (2008) are the first studies to independently observe divergent transcription from mammalian gene promoters.”
Analysis of nascent RNA identifies a unified architecture of initiation regions at mammalian promoters and enhancers (2014, neutral): “Several studies have documented divergent transcription at promoters and enhancers 2, 3, 8, 9, 38 , however, the nature and organization of initiation sites, their underlying DNA elements, and their relationships with transcription factor binding and nucleosome positions have yet to be reconciled.”
Long noncoding RNAs: functional surprises from the RNA world. (2009, background): “For example, small RNAs have been found to cluster near the 59 and 39 ends of genes (Han et al. 2007; Kapranov et al. 2007a; Core et al. 2008; He et al. 2008; Preker et al. 2008; Seila et al. 2008; Fejes-Toth et al. 2009; Neil et al. 2009; Taft et al. 2009; Xu et al. 2009).”