UHRF1

Ubiquitin-like with PHD and RING finger domains 1 (UHRF1) functions as a multidomain epigenetic regulator coordinating DNA methylation, histone modifications, and protein ubiquitination^[1][2]. Mechanistically, UHRF1 interacts with DNMT1 to maintain DNA methylation during replication and recruits histone-modifying enzymes, ensuring stable epigenetic silencing of target genes^[3][4][5]. Through these interactions, UHRF1 regulates cell cycle progression, redox homeostasis, and chromatin accessibility in diverse cell types, including vascular smooth muscle cells (VSMCs) and retinal cells^[6][7][8]. Compared with UHRF2, UHRF1 uniquely maintains daughter strand DNA methylation and interacts with a broader set of epigenetic effectors, producing distinct functional outcomes^[1][9]. In disease contexts, UHRF1 overexpression drives tumorigenesis in multiple cancers, promotes epithelial-mesenchymal transition in renal fibrosis, and mediates chemotherapy resistance via modulation of apoptotic and oxidative stress pathways^{[2][6][10][11][12][13][8]}. In vascular pathology, UHRF1 controls VSMC plasticity by repressing cell cycle inhibitors and prodifferentiation genes, linking epigenetic regulation to cardiovascular remodeling^[8]. Functionally, UHRF1 also suppresses retrotransposon activation and regulates innate immune responses, highlighting its epigenetic and non-DNA methylation-dependent roles^[12]. For experimental applications, chemical inhibitors and small molecules targeting UHRF1’s SRA or RING domains have been used to modulate DNA methylation, gene expression, and apoptosis in cellular and animal models^[14][15][16].