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RNA polymerase II pausing regulates a quiescence-dependent transcriptional program, priming cells for cell cycle reentry

Hardik P. Gala, Debarya Saha, Nisha Venugopal, Ajoy Aloysius, View ORCID ProfileJyotsna Dhawan
doi: https://doi.org/10.1101/250910
Hardik P. Gala
1Centre for Cellular and Molecular Biology, Hyderabad, 500 007 India
2Institute for Stem Cell Biology and Regenerative Medicine, Bangalore, 560065 India
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Debarya Saha
1Centre for Cellular and Molecular Biology, Hyderabad, 500 007 India
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Nisha Venugopal
1Centre for Cellular and Molecular Biology, Hyderabad, 500 007 India
2Institute for Stem Cell Biology and Regenerative Medicine, Bangalore, 560065 India
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Ajoy Aloysius
1Centre for Cellular and Molecular Biology, Hyderabad, 500 007 India
2Institute for Stem Cell Biology and Regenerative Medicine, Bangalore, 560065 India
3National Center for Biological Sciences, Bangalore, 560065 India
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Jyotsna Dhawan
1Centre for Cellular and Molecular Biology, Hyderabad, 500 007 India
2Institute for Stem Cell Biology and Regenerative Medicine, Bangalore, 560065 India
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  • ORCID record for Jyotsna Dhawan
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Abstract

Adult stem cells persist in mammalian tissues by entering a state of reversible arrest or quiescence associated with low transcription. Using cultured myoblasts and primary muscle stem cells, we show that RNA synthesis is strongly repressed in G0, returning within minutes of activation. We investigate the underlying mechanism and reveal a role for promoter-proximal RNAPol II pausing: by mapping global Pol II occupancy using ChIP-seq, in conjunction with RNA-seq to identify repressed transcriptional networks unique to G0. Strikingly, Pol II pausing is enhanced in G0 on genes encoding regulators of RNA biogenesis (Ncl, Rps24, Ctdp1), and release of pausing is critical for cell cycle re-entry. Finally, we uncover a novel, unexpected repressive role of the super-elongation complex component Aff4 in G0-specific stalling. We propose a model wherein Pol II pausing restrains transcription to maintain G0, preconfigures gene networks required for the G0-G1 transition, and sets the timing of their transcriptional activation.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted January 19, 2018.
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RNA polymerase II pausing regulates a quiescence-dependent transcriptional program, priming cells for cell cycle reentry
Hardik P. Gala, Debarya Saha, Nisha Venugopal, Ajoy Aloysius, Jyotsna Dhawan
bioRxiv 250910; doi: https://doi.org/10.1101/250910
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RNA polymerase II pausing regulates a quiescence-dependent transcriptional program, priming cells for cell cycle reentry
Hardik P. Gala, Debarya Saha, Nisha Venugopal, Ajoy Aloysius, Jyotsna Dhawan
bioRxiv 250910; doi: https://doi.org/10.1101/250910

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