XB-ART-44013J Biol Chem. December 9, 2011; 286 (49): 42221-31.
Protein arginine methyltransferase Prmt5-Mep50 methylates histones H2A and H4 and the histone chaperone nucleoplasmin in Xenopus laevis eggs.
Histone proteins carry information contained in post-translational modifications. Eukaryotic cells utilize this histone code to regulate the usage of the underlying DNA. In the maturing oocytes and eggs of the frog Xenopus laevis, histones are synthesized in bulk in preparation for deposition during the rapid early developmental cell cycles. During this key developmental time frame, embryonic pluripotent chromatin is established. In the egg, non-chromatin-bound histones are complexed with storage chaperone proteins, including nucleoplasmin. Here we describe the identification and characterization of a complex of the protein arginine methyltransferase 5 (Prmt5) and the methylosome protein 50 (Mep50) isolated from Xenopus eggs that specifically methylates predeposition histones H2A/H2A.X-F and H4 and the histone chaperone nucleoplasmin on a conserved motif (GRGXK). We demonstrate that nucleoplasmin (Npm), an exceedingly abundant maternally deposited protein, is a potent substrate for Prmt5-Mep50 and is monomethylated and symmetrically dimethylated at Arg-187. Furthermore, Npm modulates Prmt5-Mep50 activity directed toward histones, consistent with a regulatory role for Npm in vivo. We show that H2A and nucleoplasmin methylation appears late in oogenesis and is most abundant in the laid egg. We hypothesize that these very abundant arginine methylations are constrained to pre-mid blastula transition events in the embryo and therefore may be involved in the global transcriptional repression found in this developmental time frame.
PubMed ID: 22009756
PMC ID: PMC3234966
Article link: J Biol Chem.
Grant support: GM037537 NIGMS NIH HHS , GM075486 NIGMS NIH HHS , RR00862 NCRR NIH HHS , GM037537 NIGMS NIH HHS , P41 RR000862 NCRR NIH HHS , F32 GM075486 NIGMS NIH HHS , R01 GM037537 NIGMS NIH HHS , RR00862 NCRR NIH HHS , GM075486 NIGMS NIH HHS
Genes referenced: hist2h2ab npm1 prmt5 wdr77