PT  - JOURNAL ARTICLE
AU  - Hardik P. Gala
AU  - Debarya Saha
AU  - Nisha Venugopal
AU  - Ajoy Aloysius
AU  - Jyotsna Dhawan
TI  - RNA polymerase II pausing regulates a quiescence-dependent transcriptional program, priming cells for cell cycle reentry
AID  - 10.1101/250910
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 250910
4099  - http://biorxiv.org/content/early/2018/01/19/250910.short
4100  - http://biorxiv.org/content/early/2018/01/19/250910.full
AB  - 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.