title: Protein arginine methyltransferase 6 specifically methylates the nonhistone chromatin protein HMGA1a.
abstract: The HMGA family proteins HMGA1a and HMGA1b are nuclear nonhistone species implicated in a wide range of cellular processes including inducible gene transcription, modulation of chromosome structure through nucleosome and chromosome remodeling, and neoplastic transformation. HMGA proteins are highly modified, and changes in their phosphorylation states have been correlated with the phase of the cell cycle and changes in their transcriptional activity. HMGA1a is also methylated in the first DNA-binding AT-hook at Arg25 and other sites, although the enzyme or enzymes responsible have not been identified. We demonstrate here that a GST fusion of protein arginine methyltransferase 6 (PRMT6) specifically methylates full-length recombinant HMGA1a protein in vitro. Although GST fusions of PRMT1 and PRMT3 were also capable of methylating the full-length HMGA1a polypeptide, they recognize its proteolytic degradation products much better. GST fusions of PRMT4 or PRMT7 were unable to methylate the full-length protein or its degradation products. We conclude that PRMT6 is a good candidate for the endogenous enzyme responsible for HGMA1a methylation.
authors.affiliation: Department of Chemistry and Biochemistry, Molecular Biology Institute, UCLA, Los Angeles, CA 90095-1560, USA.
authors.forename: Tina Branscombe
authors.initials: TB
authors.lastname: Miranda
authors.forename: Kristofor J
authors.initials: KJ
authors.lastname: Webb
authors.forename: Dale D
authors.initials: DD
authors.lastname: Edberg
authors.forename: Raymond
authors.initials: R
authors.lastname: Reeves
authors.forename: Steven
authors.initials: S
authors.lastname: Clarke
mesh_terms: D025741:HMGA1a Protein / Q000378:metabolism*; D006801:Humans; D008745:Methylation; D009687:Nuclear Proteins / Q000378:metabolism*; D011484:Protein-Arginine N-Methyltransferases / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D009687:Nuclear Proteins; D025741:HMGA1a Protein; C447833:PRMT6 protein, human; D011484:Protein-Arginine N-Methyltransferases