Prmt5 is essential for early mouse development and acts in the cytoplasm to maintain ES cell pluripotency

Wee Wei Tee, Mercedes Pardo, Thorold W. Theunissen, Lu Yu, Jyoti S. Choudhary, Petra Hajkova, M. Azim Surani

Research output: Contribution to journalArticlepeer-review

264 Scopus citations

Abstract

Prmt5, an arginine methyltransferase, has multiple roles in germ cells, and possibly in pluripotency. Here we show that loss of Prmt5 function is early embryonic-lethal due to the abrogation of pluripotent cells in blastocysts. Prmt5 is also up-regulated in the cytoplasm during the derivation of embryonic stem (ES) cells together with Stat3, where they persist to maintain pluripotency. Prmt5 in association with Mep50 methylates cytosolic histone H2A (H2AR3me2s) to repress differentiation genes in ES cells. Loss of Prmt5 or Mep50 results in derepression of differentiation genes, indicating the significance of the Prmt5/Mep50 complex for pluripotency, which may occur in conjunction with the leukemia inhibitory factor (LIF)/Stat3 pathway.

Original languageEnglish
Pages (from-to)2772-2777
Number of pages6
JournalGenes and Development
Volume24
Issue number24
DOIs
StatePublished - Dec 15 2010

Keywords

  • Arginine methyltransferase
  • Embryonic stem cells
  • Epigenetics
  • H2A
  • Pluripotency

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