Distinct transcription kinetics of pluripotent cell states

Autor: Rui Shao, Banushree Kumar, Katja Lidschreiber, Michael Lidschreiber, Patrick Cramer, Simon J Elsässer
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Molecular Systems Biology, Vol 18, Iss 1, Pp 1-19 (2022)
Druh dokumentu: article
ISSN: 1744-4292
DOI: 10.15252/msb.202110407
Popis: Abstract Mouse embryonic stem cells (mESCs) can adopt naïve, ground, and paused pluripotent states that give rise to unique transcriptomes. Here, we use transient transcriptome sequencing (TT‐seq) to define both coding and non‐coding transcription units (TUs) in these three pluripotent states and combine TT‐seq with RNA polymerase II occupancy profiling to unravel the kinetics of RNA metabolism genome‐wide. Compared to the naïve state (serum), RNA synthesis and turnover rates are globally reduced in the ground state (2i) and the paused state (mTORi). The global reduction in RNA synthesis goes along with a genome‐wide decrease of polymerase elongation velocity, which is related to epigenomic features and alterations in the Pol II termination window. Our data suggest that transcription activity is the main determinant of steady state mRNA levels in the naïve state and that genome‐wide changes in transcription kinetics invoke ground and paused pluripotent states.
Databáze: Directory of Open Access Journals
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