RNA Pol II pausing facilitates phased pluripotency transitions by buffering transcription

Abuhashem, Abderhman, Chivu, Alexandra G, Zhao, Yixin, Rice, Edward J, Siepel, Adam, Danko, Charles G, Hadjantonakis, Anna-Katerina (August 2022) RNA Pol II pausing facilitates phased pluripotency transitions by buffering transcription. Genes and Development. ISSN 0890-9369

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Abstract

Promoter-proximal RNA Pol II pausing is a critical step in transcriptional control. Pol II pausing has been predominantly studied in tissue culture systems. While Pol II pausing has been shown to be required for mammalian development, the phenotypic and mechanistic details of this requirement are unknown. Here, we found that loss of Pol II pausing stalls pluripotent state transitions within the epiblast of the early mouse embryo. Using Nelfb -/- mice and a NELFB degron mouse pluripotent stem cell model, we show that embryonic stem cells (ESCs) representing the naïve state of pluripotency successfully initiate a transition program but fail to balance levels of induced and repressed genes and enhancers in the absence of NELF. We found an increase in chromatin-associated NELF during transition from the naïve to later pluripotent states. Overall, our work defines the acute and long-term molecular consequences of NELF loss and reveals a role for Pol II pausing in the pluripotency continuum as a modulator of cell state transitions.

Item Type:	Paper
Subjects:	bioinformatics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > transcription bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics
CSHL Authors:	Zhao, Yixin Siepel, Adam
Communities:	CSHL labs > Siepel lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	18 August 2022
Date Deposited:	30 Aug 2022 21:17
Last Modified:	11 Jan 2024 15:24
PMCID:	PMC9480856
URI:	https://repository.cshl.edu/id/eprint/40703

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