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  Conserved DNA sequence features underlie pervasive RNA polymerase pausing

Gajos, M., Jasnovidova, O., van Bömmel, A., Freier, S., Vingron, M., & Mayer, A. (2021). Conserved DNA sequence features underlie pervasive RNA polymerase pausing. Nucleic Acids Research (London), 49(8), 4402-4420. doi:10.1093/nar/gkab208.

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 Creators:
Gajos, Martyna1, Author              
Jasnovidova, Olga1, Author              
van Bömmel, Alena2, Author              
Freier, Susanne1, Author              
Vingron, Martin3, Author              
Mayer, Andreas1, Author              
Affiliations:
1Nascent Transcription and Cell Differentiation (Andreas Mayer), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_2385699              
2Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433547              
3Gene regulation (Martin Vingron), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479639              

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 Abstract: Pausing of transcribing RNA polymerase is regulated and creates opportunities to control gene expression. Research in metazoans has so far mainly focused on RNA polymerase II (Pol II) promoter-proximal pausing leaving the pervasive nature of pausing and its regulatory potential in mammalian cells unclear. Here, we developed a pause detecting algorithm (PDA) for nucleotide-resolution occupancy data and a new native elongating transcript sequencing approach, termed nested NET-seq, that strongly reduces artifactual peaks commonly misinterpreted as pausing sites. Leveraging PDA and nested NET-seq reveal widespread genome-wide Pol II pausing at single-nucleotide resolution in human cells. Notably, the majority of Pol II pauses occur outside of promoter-proximal gene regions primarily along the gene-body of transcribed genes. Sequence analysis combined with machine learning modeling reveals DNA sequence properties underlying widespread transcriptional pausing including a new pause motif. Interestingly, key sequence determinants of RNA polymerase pausing are conserved between human cells and bacteria. These studies indicate pervasive sequence-induced transcriptional pausing in human cells and the knowledge of exact pause locations implies potential functional roles in gene expression.

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Language(s): eng - English
 Dates: 2021-03-152021-03-312021-05-07
 Publication Status: Published in print
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 Identifiers: DOI: 10.1093/nar/gkab208
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Title: Nucleic Acids Research (London)
  Other : Nucleic Acids Res
Source Genre: Journal
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Publ. Info: Oxford : Oxford University Press
Pages: 19 Volume / Issue: 49 (8) Sequence Number: - Start / End Page: 4402 - 4420 Identifier: ISSN: 0305-1048
CoNE: https://pure.mpg.de/cone/journals/resource/110992357379342