| Literature DB >> 29174978 |
Melodi Tastemel1, Aishwarya A Gogate2, Venkat S Malladi2, Kim Nguyen2, Courtney Mitchell2, Laura A Banaszynski2, Xiaoying Bai3.
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.Entities:
Keywords: Global run-on sequencing (GRO-seq); Mouse embryonic stem cell; Transcription pausing
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Year: 2017 PMID： 29174978 PMCID： PMC5732849 DOI： 10.1016/j.scr.2017.11.012
Source DB: PubMed Journal: Stem Cell Res ISSN： 1873-5061 Impact factor: 2.020