RNA Pol II pausing facilitates phased pluripotency transitions by buffering transcription

Abuhashem, Abderhman, Chivu, Alexandra, Zhao, Yixin, Rice, Edward, Siepel, Adam, Danko, Charles, Hadjantonakis, Anna-Katerina (2022) RNA Pol II pausing facilitates phased pluripotency transitions by buffering transcription. bioRxiv. (Submitted)

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Abstract

Promoter-proximal RNA Pol II pausing is a critical step in transcriptional control. Pol II pausing has been studied predominantly 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 find that loss of RNA Pol II pausing stalls pluripotent state transitions in the epiblast of the early mouse embryo. Using Nelfb-/- mice and a novel NELFB- degron mouse embryonic stem cells, we show that mouse ES cells (mESCs) representing the naive 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. Consistently, we find an increase in chromatin-associated NELF during pluripotency transitions. Overall, our work reveals the molecular and phenotypic roles of Pol II pausing in pluripotency and introduces Pol II pausing 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 bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > RNA polymerase bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types
CSHL Authors:	Zhao, Yixin Siepel, Adam
Communities:	CSHL labs > Siepel lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	2022
Date Deposited:	13 Oct 2023 13:30
Last Modified:	11 Jan 2024 15:23
PMCID:	PMC9480856
Related URLs:	Publisher PubMed
URI:	https://repository.cshl.edu/id/eprint/41217

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