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Stem Cell Res. 2017 Dec;25:250-255. doi: 10.1016/j.scr.2017.11.012. Epub 2017 Nov 16.

Transcription pausing regulates mouse embryonic stem cell differentiation.

Author information

1
Cecil H. and Ida Green Center for Reproductive Biology Sciences and Division of Basic Reproductive Biology Research, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Genetics, Development and Diseases Graduate Program, University of Texas Southwestern Medical Center, Dallas, TX, USA.
2
Cecil H. and Ida Green Center for Reproductive Biology Sciences and Division of Basic Reproductive Biology Research, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
3
Cecil H. and Ida Green Center for Reproductive Biology Sciences and Division of Basic Reproductive Biology Research, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address: Xiaoying.Bai@utsouthwestern.edu.

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.

KEYWORDS:

Global run-on sequencing (GRO-seq); Mouse embryonic stem cell; Transcription pausing

PMID:
29174978
PMCID:
PMC5732849
DOI:
10.1016/j.scr.2017.11.012
[Indexed for MEDLINE]
Free PMC Article

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