RNA polymerase II pausing modulates hematopoietic stem cell emergence in zebrafish

Qiwen Yang, Xiuli Liu, Ting Zhou, Jennifer Cook, Kim Nguyen, Xiaoying Bai

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

The promoter-proximal pausing of RNA polymerase II (Pol II) plays a critical role in regulating metazoan gene transcription. Despite the prevalence of Pol II pausing across the metazoan genomes, little is known about the in vivo effect of Pol II pausing on vertebrate development. We use the emergence of hematopoietic stem cells (HSCs) in zebrafish embryos as a model to investigate the role of Pol II pausing in vertebrate organogenesis. Disrupting Pol II pausing machinery causes a severe reduction of HSC specification, a defect that can be effectively rescued by inhibiting Pol II elongation. In pausing-deficient embryos, the transforming growth factor β (TGFβ) signaling is elevated due to enhanced transcription elongation of key pathway genes, leading to HSC inhibition; in contrast, the interferon-γ (IFN-γ) signaling and its downstream effector Jak2/Stat3, which are required for HSC formation, are markedly attenuated owing to reduced chromatin accessibility on IFN-γ receptor genes. These findings reveal a novel transcription mechanism instructing HSC fate by pausing-mediated differential regulation of key signaling pathways.

Original languageEnglish (US)
Pages (from-to)1701-1710
Number of pages10
JournalBlood
Volume128
Issue number13
DOIs
StatePublished - Sep 29 2016

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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  • Cite this

    Yang, Q., Liu, X., Zhou, T., Cook, J., Nguyen, K., & Bai, X. (2016). RNA polymerase II pausing modulates hematopoietic stem cell emergence in zebrafish. Blood, 128(13), 1701-1710. https://doi.org/10.1182/blood-2016-02-697847