Targets of histone H3 lysine 9 methyltransferases

Aidan J Levinsky; Gregor McEdwards; Nasha Sethna; Mark A Currie

doi:10.3389/fcell.2022.1026406

Targets of histone H3 lysine 9 methyltransferases

Front Cell Dev Biol. 2022 Dec 6:10:1026406. doi: 10.3389/fcell.2022.1026406. eCollection 2022.

Authors

Aidan J Levinsky^#^{1

2}, Gregor McEdwards^#^{1

2}, Nasha Sethna^#^{1

2}, Mark A Currie^{1

2}

Affiliations

¹ Department of Biology, University of Toronto Mississauga, Mississauga, ON, Canada.
² Department of Cell and Systems Biology, University of Toronto, Toronto, ON, Canada.

^# Contributed equally.

Abstract

Histone H3 lysine 9 di- and trimethylation are well-established marks of constitutively silenced heterochromatin domains found at repetitive DNA elements including pericentromeres, telomeres, and transposons. Loss of heterochromatin at these sites causes genomic instability in the form of aberrant DNA repair, chromosome segregation defects, replication stress, and transposition. H3K9 di- and trimethylation also regulate cell type-specific gene expression during development and form a barrier to cellular reprogramming. However, the role of H3K9 methyltransferases extends beyond histone methylation. There is a growing list of non-histone targets of H3K9 methyltransferases including transcription factors, steroid hormone receptors, histone modifying enzymes, and other chromatin regulatory proteins. Additionally, two classes of H3K9 methyltransferases modulate their own function through automethylation. Here we summarize the structure and function of mammalian H3K9 methyltransferases, their roles in genome regulation and constitutive heterochromatin, as well as the current repertoire of non-histone methylation targets including cases of automethylation.

Keywords: chromatin; heterochromatin; histone; methylation; methyltransferase.

Publication types

Review

Grants and funding

This work was supported by the Canadian Foundation for Innovation - John R. Evans Leaders Fund, Ontario Research Fund (CFI/ORF project no. 40684), Research and Scholarly Activity Fund, and Connaught New Researcher Award funding to MAC. GM is supported by an Ontario Graduate Scholarship.