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

Research output: Contribution to journalArticle

3 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)250-255
Number of pages6
JournalStem Cell Research
Volume25
DOIs
StatePublished - Dec 1 2017

Keywords

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

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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  • Cite this

    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