Proteome-wide Prediction of Lysine Methylation Leads to Identification of H2BK43 Methylation and Outlines the Potential Methyllysine Proteome

Kyle K. Biggar; Francois Charih; Huadong Liu; Yasser B. Ruiz-Blanco; Leanne Stalker; Anand Chopra; Justin Connolly; Hemanta Adhikary; Kristin Frensemier; Matthew Hoekstra; Marek Galka; Qi Fang; Christopher Wynder; William L. Stanford; James R. Green; Shawn S.-C. Li

Cell Reports (Jul 2020)

Proteome-wide Prediction of Lysine Methylation Leads to Identification of H2BK43 Methylation and Outlines the Potential Methyllysine Proteome

Kyle K. Biggar,
Francois Charih,
Huadong Liu,
Yasser B. Ruiz-Blanco,
Leanne Stalker,
Anand Chopra,
Justin Connolly,
Hemanta Adhikary,
Kristin Frensemier,
Matthew Hoekstra,
Marek Galka,
Qi Fang,
Christopher Wynder,
William L. Stanford,
James R. Green,
Shawn S.-C. Li

Affiliations

Kyle K. Biggar: Institute of Biochemistry and Department of Biology, Carleton University, Ottawa, ON K1S 5B6, Canada
Francois Charih: Institute of Biochemistry and Department of Biology, Carleton University, Ottawa, ON K1S 5B6, Canada; Systems and Computer Engineering, Carleton University, Ottawa, ON K1S 5BS, Canada
Huadong Liu: Department of Biochemistry, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1, Canada
Yasser B. Ruiz-Blanco: Systems and Computer Engineering, Carleton University, Ottawa, ON K1S 5BS, Canada; Computational Biochemistry, Center of Medical Biotechnology, University of Duisburg, Essen, Germany
Leanne Stalker: Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada
Anand Chopra: Institute of Biochemistry and Department of Biology, Carleton University, Ottawa, ON K1S 5B6, Canada
Justin Connolly: Institute of Biochemistry and Department of Biology, Carleton University, Ottawa, ON K1S 5B6, Canada
Hemanta Adhikary: Institute of Biochemistry and Department of Biology, Carleton University, Ottawa, ON K1S 5B6, Canada
Kristin Frensemier: Institute of Biochemistry and Department of Biology, Carleton University, Ottawa, ON K1S 5B6, Canada
Matthew Hoekstra: Institute of Biochemistry and Department of Biology, Carleton University, Ottawa, ON K1S 5B6, Canada
Marek Galka: Department of Biochemistry, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1, Canada
Qi Fang: Department of Biochemistry, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1, Canada
Christopher Wynder: Department of Biochemistry, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1, Canada
William L. Stanford: Ottawa Hospital Research Institute, Sprott Center for Stem Cell Research, Ottawa, ON K1H 8L6, Canada
James R. Green: Systems and Computer Engineering, Carleton University, Ottawa, ON K1S 5BS, Canada
Shawn S.-C. Li: Department of Biochemistry, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1, Canada; Corresponding author

Journal volume & issue: Vol. 32, no. 2
p. 107896

Abstract

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Summary: Protein Lys methylation plays a critical role in numerous cellular processes, but it is challenging to identify Lys methylation in a systematic manner. Here we present an approach combining in silico prediction with targeted mass spectrometry (MS) to identify Lys methylation (Kme) sites at the proteome level. We develop MethylSight, a program that predicts Kme events solely on the physicochemical properties of residues surrounding the putative methylation sites, which then requires validation by targeted MS. Using this approach, we identify 70 new histone Kme marks with a 90% validation rate. H2BK43me2, which undergoes dynamic changes during stem cell differentiation, is found to be a substrate of KDM5b. Furthermore, MethylSight predicts that Lys methylation is a prevalent post-translational modification in the human proteome. Our work provides a useful resource for guiding systematic exploration of the role of Lys methylation in human health and disease.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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