Targeting EHMT2/G9a for cancer therapy: Progress and perspective

Euchromatic histone lysine methyltransferase-2, also known as G9a, is a ubiquitously expressed SET domain-containing histone lysine methyltransferase linked with both facultative and constitutive heterochromatin formation and transcriptional repression. It is an essential developmental gene and reported to play role in embryonic development, establishment of proviral silencing in ES cells, tumor cell growth, metastasis, T-cell immune response, cocaine induced neural plasticity and cognition and adaptive behavior. It is mainly responsible for carrying out mono, di and tri methylation of histone H3K9 in euchromatin. G9a levels are elevated in many cancers and its selective inhibition is known to reduce the cell growth and induce autophagy, apoptosis and senescence. We carried out a thorough search of online literature databases including Pubmed, Scopus, Journal websites, Clinical trials etc to gather the maximum possible information related to the G9a. The main messages from the cited papers are presented in a systematic manner. Chemical structures were drawn by Chemdraw software. In this review, we shed light on current understanding of structure and biological activity of G9a, the molecular events directing its targeting to genomic regions and its post-translational modification. Finally, we discuss the current strategies to target G9a in different cancers and evaluate the available compounds and agents used to inhibit G9a functions. The review provides the present status and future directions of research in targeting G9a and provides the basis to persuade the development of novel strategies to target G9a -related effects in cancer cells.

Automated summary

G9a, an essential histone lysine methyltransferase, is involved in various biological processes and known to be upregulated in cancer. This review aims to understand the structure, activity, and targeting strategies of G9a.