Nuclear High Mobility Group A2 (HMGA2) Interactome Revealed by Biotin Proximity Labeling

Antoine Gaudreau-Lapierre; Thomas Klonisch; Hannah Nicolas; Thatchawan Thanasupawat; Laura Trinkle-Mulcahy; Sabine Hombach-Klonisch

doi:10.3390/ijms24044246

Nuclear High Mobility Group A2 (HMGA2) Interactome Revealed by Biotin Proximity Labeling

Int J Mol Sci. 2023 Feb 20;24(4):4246. doi: 10.3390/ijms24044246.

Authors

Antoine Gaudreau-Lapierre^{1

2}, Thomas Klonisch^{3

4

5

6}, Hannah Nicolas^{1

2}, Thatchawan Thanasupawat³, Laura Trinkle-Mulcahy^{1

2}, Sabine Hombach-Klonisch^{3

4}

Affiliations

¹ Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
² Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, ON K1N 6N5, Canada.
³ Department of Human Anatomy and Cell Science, Rady Faculty of Health Sciences, College of Medicine, University of Manitoba, CancerCare Manitoba, Winnipeg, MB R3T 2N2, Canada.
⁴ Department of Pathology, Rady Faculty of Health Sciences, College of Medicine, University of Manitoba, CancerCare Manitoba, Winnipeg, MB R3T 2N2, Canada.
⁵ Department of Medical Microbiology & Infectious Diseases, Rady Faculty of Health Sciences, College of Medicine, University of Manitoba, CancerCare Manitoba, Winnipeg, MB R3T 2N2, Canada.
⁶ Research Institute in Oncology and Hematology (RIOH), CancerCare Manitoba, Winnipeg, MB R3T 2N2, Canada.

Abstract

The non-histone chromatin binding protein High Mobility Group AT-hook protein 2 (HMGA2) has important functions in chromatin remodeling, and genome maintenance and protection. Expression of HMGA2 is highest in embryonic stem cells, declines during cell differentiation and cell aging, but it is re-expressed in some cancers, where high HMGA2 expression frequently coincides with a poor prognosis. The nuclear functions of HMGA2 cannot be explained by binding to chromatin alone but involve complex interactions with other proteins that are incompletely understood. The present study used biotin proximity labeling, followed by proteomic analysis, to identify the nuclear interaction partners of HMGA2. We tested two different biotin ligase HMGA2 constructs (BioID2 and miniTurbo) with similar results, and identified known and new HMGA2 interaction partners, with functionalities mainly in chromatin biology. These HMGA2 biotin ligase fusion constructs offer exciting new possibilities for interactome discovery research, enabling the monitoring of nuclear HMGA2 interactomes during drug treatments.

Keywords: BioID; HMGA2; biotin; miniTurbo; nuclear; proximity labeling.

MeSH terms

Biotin*
Cell Differentiation
Chromatin
HMGA2 Protein*
Ligases
Proteomics*

Substances

Biotin
Chromatin
Ligases
HMGA2 Protein

Grants and funding

This research was funded by NSERC Discovery grants by L.T.-M., T.K., and S.H.-K., T.K. and S.H.-K. gratefully acknowledge the Cancer Research Society and CIHR for funding.