PHB Associates with the HIRA Complex to Control an Epigenetic-Metabolic Circuit in Human ESCs

Zhexin Zhu, Chunliang Li, Yanwu Zeng, Jianyi Ding, Zepeng Qu, Junjie Gu, Laixiang Ge, Fan Tang, Xin Huang, Chenlin Zhou, Ping Wang, Deyou Zheng, Ying Jin

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

The chromatin landscape and cellular metabolism both contribute to cell fate determination, but their interplay remains poorly understood. Using genome-wide siRNA screening, we have identified prohibitin (PHB) as an essential factor in self-renewal of human embryonic stem cells (hESCs). Mechanistically, PHB forms protein complexes with HIRA, a histone H3.3 chaperone, and stabilizes the protein levels of HIRA complex components. Like PHB, HIRA is required for hESC self-renewal. PHB and HIRA act together to control global deposition of histone H3.3 and gene expression in hESCs. Of particular note, PHB and HIRA regulate the chromatin architecture at the promoters of isocitrate dehydrogenase genes to promote transcription and, thus, production of α-ketoglutarate, a key metabolite in the regulation of ESC fate. Our study shows that PHB has an unexpected nuclear role in hESCs that is required for self-renewal and that it acts with HIRA in chromatin organization to link epigenetic organization to a metabolic circuit.

Original languageEnglish (US)
Pages (from-to)274-289.e7
JournalCell Stem Cell
Volume20
Issue number2
DOIs
StatePublished - Feb 2 2017

Keywords

  • H3.3
  • HIRA complexes
  • PHB
  • epigenetics
  • human ESCs
  • metabolism
  • self-renewal
  • α-ketoglutarate

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

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  • Cite this

    Zhu, Z., Li, C., Zeng, Y., Ding, J., Qu, Z., Gu, J., Ge, L., Tang, F., Huang, X., Zhou, C., Wang, P., Zheng, D., & Jin, Y. (2017). PHB Associates with the HIRA Complex to Control an Epigenetic-Metabolic Circuit in Human ESCs. Cell Stem Cell, 20(2), 274-289.e7. https://doi.org/10.1016/j.stem.2016.11.002