Transcription pausing regulates mouse embryonic stem cell differentiation
Melodi Tastemel, Aishwarya A. Gogate, Venkat S. Malladi, Kim Nguyen, Courtney Mitchell, Laura A. Banaszynski, Xiaoying Bai
Obstetrics & Gynecology - Chairman's Office
Children's Research Institute
Obstetrics & Gynecology - Green Center
Pediatrics - Other
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.
https://doi.org/10.1016/j.scr.2017.11.012
Global run-on sequencing (GRO-seq)
Mouse embryonic stem cell
Transcription pausing
10.1016/j.scr.2017.11.012
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Mouse Embryonic Stem Cells Medicine & Life Sciences
Embryonic Stem Cells Medicine & Life Sciences
Cell Differentiation Medicine & Life Sciences
RNA Polymerase II Medicine & Life Sciences
Epigenomics Medicine & Life Sciences
Chromatin Medicine & Life Sciences
Genome Medicine & Life Sciences
Tastemel, M., Gogate, A. A., Malladi, V. S., Nguyen, K., Mitchell, C., Banaszynski, L. A., & Bai, X. (2017). Transcription pausing regulates mouse embryonic stem cell differentiation. Stem Cell Research, 25, 250-255. https://doi.org/10.1016/j.scr.2017.11.012
Transcription pausing regulates mouse embryonic stem cell differentiation. / Tastemel, Melodi; Gogate, Aishwarya A.; Malladi, Venkat S.; Nguyen, Kim; Mitchell, Courtney; Banaszynski, Laura A.; Bai, Xiaoying.
In: Stem Cell Research, Vol. 25, 12.2017, p. 250-255.
Tastemel, M, Gogate, AA, Malladi, VS, Nguyen, K, Mitchell, C, Banaszynski, LA & Bai, X 2017, 'Transcription pausing regulates mouse embryonic stem cell differentiation', Stem Cell Research, vol. 25, pp. 250-255. https://doi.org/10.1016/j.scr.2017.11.012
Tastemel M, Gogate AA, Malladi VS, Nguyen K, Mitchell C, Banaszynski LA et al. Transcription pausing regulates mouse embryonic stem cell differentiation. Stem Cell Research. 2017 Dec;25:250-255. https://doi.org/10.1016/j.scr.2017.11.012
Tastemel, Melodi ; Gogate, Aishwarya A. ; Malladi, Venkat S. ; Nguyen, Kim ; Mitchell, Courtney ; Banaszynski, Laura A. ; Bai, Xiaoying. / Transcription pausing regulates mouse embryonic stem cell differentiation. In: Stem Cell Research. 2017 ; Vol. 25. pp. 250-255.
@article{24e5ba6193ae409f9773461dffcb8647,
title = "Transcription pausing regulates mouse embryonic stem cell differentiation",
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",
author = "Melodi Tastemel and Gogate, {Aishwarya A.} and Malladi, {Venkat S.} and Kim Nguyen and Courtney Mitchell and Banaszynski, {Laura A.} and Xiaoying Bai",
note = "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. ",
doi = "10.1016/j.scr.2017.11.012",
journal = "Stem Cell Research",
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.
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
U2 - 10.1016/j.scr.2017.11.012
DO - 10.1016/j.scr.2017.11.012
JO - Stem Cell Research
JF - Stem Cell Research