Opto-Epigenetic Regulation of Histone Arginine Asymmetric Dimethylation via Type I Protein Arginine Methyltransferase Inhibition.

ABSTRACT: Histone arginine asymmetric dimethylation, which is mainly catalyzed by type I protein arginine methyltransferases (PRMTs), is involved in broad biological and pathological processes. Recently, several type I PRMT inhibitors, such as MS023, have been developed to reverse the histone arginine dimethylation status in tumor cells, but extensive inhibition of type I PRMTs may cause side effects in normal tissues. Herein, we designed a photoactivatable MS023 prodrug (C-MS023) to achieve spatiotemporal inhibition of histone arginine asymmetric dimethylation. In vitro studies showed that C-MS023 exhibited reduced potency in inhibiting type I PRMTs. Importantly, visible light irradiation at 420 nm could trigger the photolysis of the prodrug, thereby liberating MS023 for effective downregulation of

SUBMITTER: Xu S 

PROVIDER: S-EPMC11873949 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature