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 numerous 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 like epithelial-mesenchymal transition, cell migration, and invasion. Its importance is underscored in multiple diseases, including cancer, fibrosis, and eye-related disorders [4,5,6,7]. Genetic models, especially knockout (KO) and conditional knockout (CKO) mouse models, are valuable tools for studying its functions.

In microglia, Yy1 lactylation at lysine 183 (K183) promoted by p300 upregulates FGF2 expression, thus accelerating angiogenesis in retinal neovascularization. Inhibiting this process could potentially be a new therapeutic target for proliferative retinopathies [1]. In M2 macrophages in prostate cancer, YY1 was highly expressed and promoted cancer progression by upregulating IL-6. Targeting YY1 in M2 macrophages suppressed cancer cell metastasis [2]. In autoimmune uveitis, increased Yy1 lactylation in retinal microglia boosted microglial activation, proliferation, and migration. Inhibiting p300, the writer of Yy1 lactylation, decreased microglial inflammation [3]. In alveolar epithelial cells, upregulation of Yy1 was associated with TGF-β-induced epithelial-mesenchymal transition (EMT) and pro-fibrosis, and knockdown of Yy1 abrogated this induction [4].

In summary, Yy1 is a multifunctional transcription factor crucial for various biological processes. Model-based research, especially using KO/CKO mouse models, has revealed its significant roles in diseases such as eye diseases, cancer, and autoimmune uveitis. Understanding Yy1 functions provides potential therapeutic targets for these disease areas.

References:

1. Wang, Xiaotang, Fan, Wei, Li, Na, Lu, Qi, Hou, Shengping. 2023. YY1 lactylation in microglia promotes angiogenesis through transcription activation-mediated upregulation of FGF2. In Genome biology, 24, 87. doi:10.1186/s13059-023-02931-y. https://pubmed.ncbi.nlm.nih.gov/37085894/

2. Chen, Saisai, Lu, Kai, Hou, Yue, Chen, Ming, Xu, Bin. . YY1 complex in M2 macrophage promotes prostate cancer progression by upregulating IL-6. In Journal for immunotherapy of cancer, 11, . doi:10.1136/jitc-2022-006020. https://pubmed.ncbi.nlm.nih.gov/37094986/

3. Huang, Jiaxing, Wang, Xiaotang, Li, Na, Yang, Peizeng, Hou, Shengping. 2024. YY1 Lactylation Aggravates Autoimmune Uveitis by Enhancing Microglial Functions via Inflammatory Genes. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 11, e2308031. doi:10.1002/advs.202308031. https://pubmed.ncbi.nlm.nih.gov/38493498/

4. Zhang, Chuyi, Zhu, Xiaoping, Hua, Yifei, Lin, Xin, Yu, Zuoren. 2019. YY1 mediates TGF-β1-induced EMT and pro-fibrogenesis in alveolar epithelial cells. In Respiratory research, 20, 249. doi:10.1186/s12931-019-1223-7. https://pubmed.ncbi.nlm.nih.gov/31703732/

5. Wang, Wenmeng, Qiao, Shiyao, Li, Guangyue, Li, Dangdang, Sui, Guangchao. . A histidine cluster determines YY1-compartmentalized coactivators and chromatin elements in phase-separated enhancer clusters. In Nucleic acids research, 50, 4917-4937. doi:10.1093/nar/gkac233. https://pubmed.ncbi.nlm.nih.gov/35390165/

6. Wang, Xiao-Li, Li, Jing, Cao, Yan-Hua. . Crosstalk between YY1 and lncRNAs in cancer: A review. In Medicine, 101, e31990. doi:10.1097/MD.0000000000031990. https://pubmed.ncbi.nlm.nih.gov/36626426/

7. Wang, Wenmeng, Li, Dangdang, Sui, Guangchao. . YY1 Is an Inducer of Cancer Metastasis. In Critical reviews in oncogenesis, 22, 1-11. doi:10.1615/CritRevOncog.2017021314. https://pubmed.ncbi.nlm.nih.gov/29604932/