Methylation-dependent SUMOylation of the architectural transcription factor HMGA2

Marianne Stabell; Thomas Sæther; Åsmund K Røhr; Odd S Gabrielsen; Ola Myklebost

doi:10.1016/j.bbrc.2021.02.099

Methylation-dependent SUMOylation of the architectural transcription factor HMGA2

Biochem Biophys Res Commun. 2021 May 7:552:91-97. doi: 10.1016/j.bbrc.2021.02.099. Epub 2021 Mar 18.

Authors

Marianne Stabell¹, Thomas Sæther², Åsmund K Røhr², Odd S Gabrielsen², Ola Myklebost³

Affiliations

¹ Department of Tumor Biology, Institute for Cancer Research, Radiumhospitalet, Oslo University Hospital, PO Box 4953 Nydalen, N-0424, Oslo, Norway; Department of Molecular Biosciences, University of Oslo, PO Box 1066 Blindern, N-0316, Oslo, Norway.
² Department of Molecular Biosciences, University of Oslo, PO Box 1066 Blindern, N-0316, Oslo, Norway.
³ Department of Tumor Biology, Institute for Cancer Research, Radiumhospitalet, Oslo University Hospital, PO Box 4953 Nydalen, N-0424, Oslo, Norway; Department of Molecular Biosciences, University of Oslo, PO Box 1066 Blindern, N-0316, Oslo, Norway. Electronic address: ola.myklebost@uib.no.

PMID: 33744765
DOI: 10.1016/j.bbrc.2021.02.099

Abstract

High mobility group A2 (HMGA2) is a chromatin-associated protein involved in the regulation of stem cell function, embryogenesis and cancer development. Although the protein does not contain a consensus SUMOylation site, it is shown to be SUMOylated. In this study, we demonstrate that the first lysine residue in the reported K₆₆KAE SUMOylation motif in HMGA2 can be methylated in vitro and in vivo by the Set7/9 methyltransferase. By editing the lysine, the increased hydrophobicity of the resulting 6-N-methyl-lysine transforms the sequence into a consensus SUMO motif. This post-translational editing dramatically increases the subsequent SUMOylation of this site. Furthermore, similar putative methylation-dependent SUMO motifs are found in a number of other chromatin factors, and we confirm methylation-dependent SUMOylation of a site in one such protein, the Polyhomeotic complex 1 homolog (PHC1). Together, these results suggest that crosstalk between methylation and SUMOylation is a general mode for regulation of chromatin function.

Keywords: HMGA2; Lysine methylation; PHC1; PML; SET7/9; SUMOylation; Ubc9.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Motifs / genetics
Amino Acid Sequence
Binding Sites / genetics
Cell Line
HMGA2 Protein / chemistry
HMGA2 Protein / genetics
HMGA2 Protein / metabolism*
Humans
Lysine / chemistry
Lysine / genetics
Lysine / metabolism*
Methylation
Protein Binding
Protein Domains
Sequence Homology, Amino Acid
Sumoylation
Transcription Factors / chemistry
Transcription Factors / genetics
Transcription Factors / metabolism*
Ubiquitin-Conjugating Enzymes / chemistry
Ubiquitin-Conjugating Enzymes / genetics
Ubiquitin-Conjugating Enzymes / metabolism

Substances

HMGA2 Protein
Transcription Factors
Ubiquitin-Conjugating Enzymes
ubiquitin-conjugating enzyme UBC9
Lysine