Ehmt2-flox Mouse

Ehmt2, also known as euchromatic histone lysine methyltransferase 2 or G9a, is a SET domain-containing histone lysine methyltransferase. It is mainly responsible for mono, di and tri methylation of histone H3K9 in euchromatin, playing a role in transcriptional regulation, genome methylation and other processes. It is an essential developmental gene involved in embryonic development, establishment of proviral silencing in ES cells, and is associated with many biological functions and diseases [3,4].

In microsatellite stability (MSS) colorectal cancer, EHMT2 inhibition can transform the immunosuppressive microenvironment into an immunomodulatory one, leading to T-cell-mediated cytotoxicity activation and improved responsiveness to anti-PD1 treatment. Mechanistically, EHMT2 forms a cotranscriptional silencing complex with CHD4 to repress galectin-7 expression, and galectin-7 up-regulation upon EHMT2 inhibition can convert a "cold" tumor environment into a T-cell-inflamed one [1].

In non-small cell lung cancer, EHMT2-mediated transcriptional reprogramming drives neuroendocrine transformation, increasing methylation of the SFRP1 promoter region to reduce SFRP1 expression, followed by activation of the WNT/β-catenin pathway. Suppression of EHMT2 with selective inhibitors can restore the sensitivity of neuroendocrine transformation cell lines to erlotinib [2].

In GNAQ/11 -mutant uveal melanoma, EHMT2 promotes tumorigenesis via ARHGAP29-mediated RhoA pathway. Inhibition of EHMT2 expression or activity significantly reduces the proliferation and migration capacity of cancer cells [5].

In conclusion, Ehmt2 is a crucial epigenetic regulator involved in multiple disease-related biological processes. Its functions in cancers such as MSS colorectal cancer, non-small cell lung cancer, and uveal melanoma are revealed through various functional studies. The research on Ehmt2 provides potential therapeutic targets for these diseases, emphasizing the importance of understanding its role in disease mechanisms for developing effective treatment strategies.