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G9a: An Emerging Epigenetic Target for Melanoma Therapy

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Journal Epigenomes
Date 2021 Oct 25
PMID 34691767
Citations 5
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Abstract

Epigenetic regulation is a crucial component of DNA maintenance and cellular identity. As our understanding of the vast array of proteins that contribute to chromatin accessibility has advanced, the role of epigenetic remodelers in disease has become more apparent. G9a is a histone methyltransferase that contributes to immune cell differentiation and function, neuronal development, and has been implicated in diseases, including cancer. In melanoma, recurrent mutations and amplifications of G9a have led to its identification as a therapeutic target. The pathways that are regulated by G9a provide an insight into relevant biomarkers for patient stratification. Future work is aided by the breadth of literature on G9a function during normal differentiation and development, along with similarities to EZH2, another histone methyltransferase that forms a synthetic lethal relationship with members of the SWI/SNF complex in certain cancers. Here, we review the literature on G9a, its role in melanoma, and lessons from EZH2 inhibitor studies.

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References
1.
Kato S, Weng Q, Insco M, Chen K, Muralidhar S, Pozniak J . Gain-of-Function Genetic Alterations of G9a Drive Oncogenesis. Cancer Discov. 2020; 10(7):980-997. PMC: 7334057. DOI: 10.1158/2159-8290.CD-19-0532. View

2.
Helming K, Wang X, Wilson B, Vazquez F, Haswell J, Manchester H . ARID1B is a specific vulnerability in ARID1A-mutant cancers. Nat Med. 2014; 20(3):251-4. PMC: 3954704. DOI: 10.1038/nm.3480. View

3.
Bergin C, Zouggar A, Haebe J, Masibag A, Desrochers F, Reilley S . G9a controls pluripotent-like identity and tumor-initiating function in human colorectal cancer. Oncogene. 2020; 40(6):1191-1202. PMC: 7878189. DOI: 10.1038/s41388-020-01591-7. View

4.
Golan T, Levy C . Negative Regulatory Loop between Microphthalmia-Associated Transcription Factor (MITF) and Notch Signaling. Int J Mol Sci. 2019; 20(3). PMC: 6387231. DOI: 10.3390/ijms20030576. View

5.
Barski A, Cuddapah S, Cui K, Roh T, Schones D, Wang Z . High-resolution profiling of histone methylations in the human genome. Cell. 2007; 129(4):823-37. DOI: 10.1016/j.cell.2007.05.009. View