Potential Therapeutics Targeting Upstream Regulators and Interactors of EHMT1/2

SIMPLE SUMMARY: The expression of Euchromatin histone lysine methyltransferase 1 and 2 (EHMT1/2) is deregulated in many cancers. Most studies thus far have focused on the downstream targets and pathways regulated by EHMTs. However, the mechanisms that lead to their deregulated expression, and the interacting proteins that could impact EHMT activity are not well understood. In this review, we summarize our current understanding of the upstream regulators and the interactors that provide alternative therapeutic approaches to tackle EHMT driven malignancies. ABSTRACT: Euchromatin histone lysine methyltransferases (EHMTs) are epigenetic regulators responsible for silencing gene transcription by catalyzing H3K9 dimethylation. Dysregulation of EHMT1/2 has been reported in multiple cancers and is associated with poor clinical outcomes. Although substantial insights have been gleaned into the downstream targets and pathways regulated by EHMT1/2, few studies have uncovered mechanisms responsible for their dysregulated expression. Moreover, EHMT1/2 interacting partners, which can influence their function and, therefore, the expression of target genes, have not been extensively explored. As none of the currently available EHMT inhibitors have made it past clinical trials, understanding upstream regulators and EHMT protein complexes may provide unique insights into novel therapeutic avenues in EHMT-overexpressing cancers. Here, we review our current understanding of the regulators and interacting partners of EHMTs. We also discuss available therapeutic drugs that target the upstream regulators and binding partners of EHMTs and could potentially modulate EHMT function in cancer progression.