Prmt5 is essential for early mouse development and acts in the cytoplasm to maintain ES cell pluripotency
- Wee-Wei Tee1,
- Mercedes Pardo2,
- Thorold W. Theunissen1,
- Lu Yu2,
- Jyoti S. Choudhary2,
- Petra Hajkova3 and
- M. Azim Surani1,4
- 1Wellcome Trust, Cancer Research UK, Gurdon Institute of Cancer and Developmental Biology, University of Cambridge, Cambridge CB2 1QN, United Kingdom;
- 2Proteomic Mass Spectrometry, Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdom;
- 3MRC Clinical Sciences Centre, Imperial College, London W12 0NN, United Kingdom
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.
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Footnotes
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↵4 Corresponding author.
E-MAIL a.surani{at}gurdon.cam.ac.uk; FAX 44-1223-334089.
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.606110.
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Supplemental material is available for this article.
- Received August 21, 2010.
- Accepted November 1, 2010.
- Copyright © 2010 by Cold Spring Harbor Laboratory Press
