RNA Pol II pausing facilitates phased pluripotency transitions by buffering transcription
Year: 2022
Type: preprint
Abstract: 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.
Source: Genes & Development
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Funders: National Aeronautics and Space Administration, National Institutes of Health, Weill Cornell Medical College, National Human Genome Research Institute, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Mapping RNA polymerase in tissue samples with ChRO-seq., G1456250384, The gut endoderm: origin, formation and fate, Dissecting the Role of RNA Pol II Pausing in Early Mammalian Development, G3376477779, Phenotyping Early Embryonic Lethal Knockout Mice to Identify Essential Genes with Previously Uncharacterized Roles in Pre-implantation Development, Gastrulation, Turning, and Placentation, Evolution of Chromatin Architecture and Transcriptional Regulation in Mammals, G566041314, Weill Cornell/Rockefeller/Sloan Kettering MST Program, Cancer Center Support Grant, Evolutionary Human Genomics: Demography, Natural Selection, and Transcriptional Regulation, Decoding cell states and tissue morphogenesis in the early mammalian embryo, G984684530
OpenAlex ID: W4292212893