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 - 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 -