title: Prmt5 is essential for early mouse development and acts in the cytoplasm to maintain ES cell pluripotency.
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.
authors.affiliation: Wellcome Trust, Cancer Research UK, Gurdon Institute of Cancer and Developmental Biology, University of Cambridge, Cambridge CB2 1QN, United Kingdom.
authors.forename: Wee-Wei
authors.initials: WW
authors.lastname: Tee
authors.forename: Mercedes
authors.initials: M
authors.lastname: Pardo
authors.forename: Thorold W
authors.initials: TW
authors.lastname: Theunissen
authors.forename: Lu
authors.initials: L
authors.lastname: Yu
authors.forename: Jyoti S
authors.initials: JS
authors.lastname: Choudhary
authors.forename: Petra
authors.initials: P
authors.lastname: Hajkova
authors.forename: M Azim
authors.initials: MA
authors.lastname: Surani
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D003593:Cytoplasm / Q000737:chemistry; D047108:Embryonic Development; D053595:Embryonic Stem Cells / Q000166:cytology*; D018507:Gene Expression Regulation, Developmental; D006657:Histones / Q000378:metabolism; D008745:Methylation; D051379:Mice; D039904:Pluripotent Stem Cells / Q000166:cytology*; D011496:Protein Methyltransferases / Q000502:physiology*; D011484:Protein-Arginine N-Methyltransferases
chemical_list: D006657:Histones; D011496:Protein Methyltransferases; C498518:Prmt5 protein, mouse; D011484:Protein-Arginine N-Methyltransferases