1. Transcription pausing regulates mouse embryonic stem cell differentiation.
- Author
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Tastemel M, Gogate AA, Malladi VS, Nguyen K, Mitchell C, Banaszynski LA, and Bai X
- Subjects
- Animals, Chromatin metabolism, Chromosomal Proteins, Non-Histone genetics, Chromosomal Proteins, Non-Histone metabolism, Histones metabolism, Mice, Mouse Embryonic Stem Cells metabolism, Promoter Regions, Genetic, RNA Polymerase II genetics, RNA Polymerase II metabolism, Transcriptional Elongation Factors genetics, Transcriptional Elongation Factors metabolism, Cell Differentiation, Mouse Embryonic Stem Cells cytology, Transcription, Genetic
- Abstract
The pluripotency of embryonic stem cells (ESCs) relies on appropriate responsiveness to developmental cues. Promoter-proximal pausing of RNA polymerase II (Pol II) has been suggested to play a role in keeping genes poised for future activation. To identify the role of Pol II pausing in regulating ESC pluripotency, we have generated mouse ESCs carrying a mutation in the pause-inducing factor SPT5. Genomic studies reveal genome-wide reduction of paused Pol II caused by mutant SPT5 and further identify a tight correlation between pausing-mediated transcription effect and local chromatin environment. Functionally, this pausing-deficient SPT5 disrupts ESC differentiation upon removal of self-renewal signals. Thus, our study uncovers an important role of Pol II pausing in regulating ESC differentiation and suggests a model that Pol II pausing coordinates with epigenetic modification to influence transcription during mESC differentiation., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2017
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