TY - JOUR
T1 - Transcription pausing regulates mouse embryonic stem cell differentiation
AU - Tastemel, Melodi
AU - Gogate, Aishwarya A.
AU - Malladi, Venkat S.
AU - Nguyen, Kim
AU - Mitchell, Courtney
AU - Banaszynski, Laura A.
AU - Bai, Xiaoying
N1 - Funding Information:
This work was supported by the National Institutes of Health ( R00DK088963 and R01DK105287 ) (X. B.), the Cancer Prevention Research Institute of Texas ( R1115 for X. B. and RR140042 for L. A. B.) and the Cecil H. and Ida Green Center Training Program in Reproductive Biology Sciences Research at UTSW. The authors declare no competing financial interests.
Publisher Copyright:
© 2017 The Authors
PY - 2017/12
Y1 - 2017/12
N2 - 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.
AB - 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.
KW - Global run-on sequencing (GRO-seq)
KW - Mouse embryonic stem cell
KW - Transcription pausing
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U2 - 10.1016/j.scr.2017.11.012
DO - 10.1016/j.scr.2017.11.012
M3 - Article
C2 - 29174978
AN - SCOPUS:85034809693
SN - 1873-5061
VL - 25
SP - 250
EP - 255
JO - Stem Cell Research
JF - Stem Cell Research
ER -