Yy1, also known as Yin Yang 1, is a transcription factor belonging to the GLI-Kruppel family of zinc finger proteins. It plays vital roles in multiple biological processes such as cell proliferation, differentiation, and apoptosis. It can either activate or repress gene expression depending on the cellular context and is involved in various pathways, including those related to tumorigenesis, angiogenesis, and inflammation [5,6,7]. Genetic models, like KO/CKO mouse models, are valuable for studying its functions.

In microglia, Yy1 lactylation at lysine 183 promotes angiogenesis by upregulating FGF2 expression, contributing to retinal neovascularization. Inhibition of p300, the regulator of Yy1 lactylation, suppresses vascularization [1]. In M2 macrophages of prostate cancer, Yy1 is highly expressed, promoting tumor progression by upregulating IL-6. Targeting Yy1 in M2 macrophages can suppress cancer cell metastasis [2]. In autoimmune uveitis, increased Yy1 lactylation in retinal microglia boosts microglial activation, proliferation, and migration by regulating inflammatory genes. Inhibiting p300 reduces Yy1 lactylation and microglial inflammation [3]. In alveolar epithelial cells, Yy1 mediates TGF-β1-induced epithelial-mesenchymal transition (EMT) and pro-fibrogenesis, and the NF-κB-Yy1 signaling pathway regulates pulmonary fibrotic progression [4].

In conclusion, Yy1 is a multifunctional transcription factor with essential roles in angiogenesis, tumor progression, inflammation, and fibrosis. Studies using KO/CKO mouse models have revealed its specific functions in these disease-related processes, providing potential therapeutic targets for proliferative retinopathies, prostate cancer, autoimmune uveitis, and pulmonary fibrosis.