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Conserved DNA sequence features underlie pervasive RNA polymerase pausing

MPS-Authors
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Gajos,  Martyna
Nascent Transcription and Cell Differentiation (Andreas Mayer), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Jasnovidova,  Olga
Nascent Transcription and Cell Differentiation (Andreas Mayer), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

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van Bömmel,  Alena
Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Freier,  Susanne
Nascent Transcription and Cell Differentiation (Andreas Mayer), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Vingron,  Martin
Gene regulation (Martin Vingron), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Mayer,  Andreas
Nascent Transcription and Cell Differentiation (Andreas Mayer), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

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NAR_Gajos_2021.pdf
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NAR_Gajos_2021Suppl.zip
(Publisher version), 4MB

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Citation

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.


Cite as: http://hdl.handle.net/21.11116/0000-0008-7DFB-2
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.