Transcription pausing regulates mouse embryonic stem cell differentiation.

Authors :: Tastemel M
Gogate AA
Malladi VS
Nguyen K
Mitchell C
Banaszynski LA
Bai X
Source :: Stem cell research [Stem Cell Res] 2017 Dec; Vol. 25, pp. 250-255. Date of Electronic Publication: 2017 Nov 16.
Publication Year :: 2017
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.<br /> (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)