The AT-hook of the chromatin architectural transcription factor high mobility group A1a is arginine-methylated by protein arginine methyltransferase 6.
The HMGA1a protein belongs to the high mobility group A (HMGA) family of architectural nuclear factors, a group of proteins that plays an important role in chromatin dynamics. HMGA proteins are multifunctional factors that associate both with DNA and nuclear proteins that have been involved in several nuclear processes, such as transcriptional regulation, viral integration, DNA repair, RNA processing, and chromatin remodeling. The activity of HMGA proteins is finely modulated by a variety of post-translational modifications. Arginine methylation was recently demonstrated to occur on HMGA1a protein, and it correlates with the apoptotic process and neoplastic progression. Methyltransferases responsible for these modifications are unknown. Here we show that the protein arginine methyltransferase PRMT6 specifically methylates HMGA1a protein both in vitro and in vivo. By mass spectrometry, the sites of methylation were unambiguously mapped to Arg(57) and Arg(59), two residues which are embedded in the second AT-hook, a region critical for both protein-DNA and protein-protein interactions and whose modification may cause profound alterations in the HMGA network. The in vivo association of HMGA and PRMT6 place this yet functionally uncharacterized methyltransferase in the well established functional context of the chromatin structure organization.
Sgarra
Riccardo
R
Dipartimento di Biochimica, Biofisica e Chimica delle Macromolecole, University of Trieste, Italy.
Lee
Jaeho
J
Tessari
Michela A
MA
Altamura
Sandro
S
Spolaore
Barbara
B
Giancotti
Vincenzo
V
Bedford
Mark T
MT
Manfioletti
Guidalberto
G
D017209:Apoptosis; D001120:Arginine / Q000378:metabolism; D002460:Cell Line; D002843:Chromatin / Q000737:chemistry*; D025741:HMGA1a Protein / Q000737:chemistry*; D006801:Humans; D013058:Mass Spectrometry; D008745:Methylation; D009687:Nuclear Proteins / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D011484:Protein-Arginine N-Methyltransferases / Q000502:physiology*; D014157:Transcription Factors / Q000737:chemistry*
D002843:Chromatin; D009687:Nuclear Proteins; D014157:Transcription Factors; D025741:HMGA1a Protein; D001120:Arginine; C447833:PRMT6 protein, human; D011484:Protein-Arginine N-Methyltransferases