{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nGLIS2 is a Krüppel‐like zinc finger transcription factor that localizes to the nucleus and acts as a bifunctional regulator, harboring both transcriptional activation and repression domains. It participates in developmental processes such as kidney morphogenesis and neuronal differentiation by modulating target gene expression through its ability to bind a consensus Glis binding sequence. In several studies, its activation function is counterbalanced by repressor domains, with its net activity being influenced by post‐translational modifications that affect DNA binding."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the kidney, GLIS2 is critical for maintaining normal architecture and function. Experimental models show that loss of GLIS2 leads to progressive chronic kidney disease with features of nephronophthisis, including tubular atrophy, fibrosis, and inflammatory infiltration. Additionally, GLIS2 has been implicated in cilia‐dependent signaling pathways, where its dysregulation contributes to cyst formation and polycystic kidney disease."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond kidney development, GLIS2 plays a role in cell fate decisions in diverse settings. For instance, in acute myelogenous leukemia models, repression of GLIS2 by Polycomb components is essential for maintaining stem cell self‐renewal, whereas overexpression prompts differentiation of AML cells. Similarly, in the testis, its interplay with the TGR5 and TP53 pathways affects germ cell apoptosis following chemotherapeutic injury. Moreover, a long noncoding RNA named “Glis2” (distinct from the protein‐coding gene) has been shown to protect podocytes from mitochondrial dysfunction and apoptosis in diabetic nephropathy through a competing endogenous RNA mechanism."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "10"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "E Lamar, C Kintner, M Goulding "}, {"type": "b", "children": [{"type": "t", "text": "Identification of NKL, a novel Gli-Kruppel zinc-finger protein that promotes neuronal differentiation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Development (2001)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/dev.128.8.1335"}], "href": "https://doi.org/10.1242/dev.128.8.1335"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11262234"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11262234"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Feng Zhang, Gen Nakanishi, Shogo Kurebayashi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of Glis2, a novel gene encoding a Gli-related, Krüppel-like transcription factor with transactivation and repressor functions. Roles in kidney development and neurogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M108062200"}], "href": "https://doi.org/10.1074/jbc.M108062200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11741991"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11741991"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Shivakumar Vasanth, Gary ZeRuth, Hong Soon Kang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of nuclear localization, DNA binding, and transactivating mechanisms of Kruppel-like zinc finger protein Gli-similar 2 (Glis2)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.165951"}], "href": "https://doi.org/10.1074/jbc.M110.165951"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21127075"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21127075"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yong-Sik Kim, Hong Soon Kang, Ronald Herbert, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Kruppel-like zinc finger protein Glis2 is essential for the maintenance of normal renal functions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.01722-07"}], "href": "https://doi.org/10.1128/MCB.01722-07"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18227149"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18227149"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Dongmei Lu, Alysha Rauhauser, Binghua Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of Glis2/NPHP7 causes kidney epithelial cell senescence and suppresses cyst growth in the Kif3a mouse model of cystic kidney disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Kidney Int (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.kint.2016.03.006"}], "href": "https://doi.org/10.1016/j.kint.2016.03.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27181777"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27181777"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Haoye Zhang, Pengcheng Zhou, Wu Xing, et al. "}, {"type": "b", "children": [{"type": "t", "text": "GLIS2 Prevents Hepatic Fibrosis by Competitively Binding HDAC3 to Inhibit Hepatic Stellate Cell Activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Mol Gastroenterol Hepatol (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jcmgh.2022.10.015"}], "href": "https://doi.org/10.1016/j.jcmgh.2022.10.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36397300"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36397300"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Chao Zhang, Michael Rehman, Xin Tian, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Glis2 is an early effector of polycystin signaling and a target for therapy in polycystic kidney disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-024-48025-6"}], "href": "https://doi.org/10.1038/s41467-024-48025-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38693102"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38693102"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Haruko Shima, Emi Takamatsu-Ichihara, Mika Shino, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ring1A and Ring1B inhibit expression of Glis2 to maintain murine "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "MOZ-TIF2"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " AML stem cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2017-05-787226"}], "href": "https://doi.org/10.1182/blood-2017-05-787226"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29371181"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29371181"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Laura Thirouard, Hélène Holota, Mélusine Monrose, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of a Crosstalk among TGR5, GLIS2, and TP53 Signaling Pathways in the Control of Undifferentiated Germ Cell Homeostasis and Chemoresistance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Adv Sci (Weinh) (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/advs.202200626"}], "href": "https://doi.org/10.1002/advs.202200626"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35435331"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35435331"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Ting Wang, Yanxia Chen, Zhihong Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long noncoding RNA Glis2 regulates podocyte mitochondrial dysfunction and apoptosis in diabetic nephropathy via sponging miR-328-5p."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Mol Med (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jcmm.18204"}], "href": "https://doi.org/10.1111/jcmm.18204"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38506068"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38506068"}]}]}]}