Tcf3, also known as transcription factor 3 or E2A, is a pivotal transcription factor. It contributes to early lymphocyte differentiation, is involved in the B-cell receptor (BCR) signaling pathway, and plays a role in embryogenesis [2,6,9]. Tcf3 is also a member of the TCF/LEF family, with impacts on tumorigenesis, and is associated with the Wnt signaling pathway [7,8]. Genetic models, such as KO mouse models, are valuable for studying its functions.

In mice, Tcf3 haploinsufficiency leads to a reduction in circulating B cells but overall normal humoral immune responses, indicating its role in lymphocyte development [2]. In mouse oocytes and early embryos, Tcf3 is identified as a key folliculogenesis regulator, with its deficiency impairing activation of key oocyte genes [1]. In CD8+ T-cell exhaustion, Id2 disrupts the assembly of the Tcf3-LSD1 complex, modulating chromatin accessibility at the Slamf6 promoter and influencing the generation of progenitor exhausted (Texprog) cells [3].

In conclusion, Tcf3 is crucial for lymphocyte development, folliculogenesis, and CD8+ T-cell exhaustion. The use of KO mouse models has significantly advanced our understanding of Tcf3's role in immunodeficiency, ovarian function, and tumor immune evasion. Additionally, Tcf3's associations with cancer, such as in leukemia and glioma, highlight its importance in disease-related research [1,2,3,4,5,7,8].

References:

1. Liu, Bofeng, He, Yuanlin, Wu, Xiaotong, Li, Jing, Xie, Wei. 2024. Mapping putative enhancers in mouse oocytes and early embryos reveals TCF3/12 as key folliculogenesis regulators. In Nature cell biology, 26, 962-974. doi:10.1038/s41556-024-01422-x. https://pubmed.ncbi.nlm.nih.gov/38839978/

2. Boast, Brigette, Goel, Shubham, González-Granado, Luis I, Kuehn, Hye Sun, Rosenzweig, Sergio D. 2023. TCF3 haploinsufficiency defined by immune, clinical, gene-dosage, and murine studies. In The Journal of allergy and clinical immunology, 152, 736-747. doi:10.1016/j.jaci.2023.05.017. https://pubmed.ncbi.nlm.nih.gov/37277074/

3. Li, Yiming, Han, Mingwei, Wei, Haolin, Zhu, Ping, Chen, Liang. 2024. Id2 epigenetically controls CD8+ T-cell exhaustion by disrupting the assembly of the Tcf3-LSD1 complex. In Cellular & molecular immunology, 21, 292-308. doi:10.1038/s41423-023-01118-6. https://pubmed.ncbi.nlm.nih.gov/38287103/

4. Salim, Mustafa, Heldt, Frederik, Thomay, Kathrin, Schlegelberger, Brigitte, Göhring, Gudrun. 2021. Cryptic TCF3 fusions in childhood leukemia: Detection by RNA sequencing. In Genes, chromosomes & cancer, 61, 22-26. doi:10.1002/gcc.22998. https://pubmed.ncbi.nlm.nih.gov/34460133/

5. Zerkalenkova, Elena, Menchits, Yaroslav, Borkovskaia, Alexandra, Karachunskii, Alexander, Olshanskaya, Yulia. 2023. TCF3 gene rearrangements in pediatric B-cell acute lymphoblastic leukemia-A single center experience. In International journal of laboratory hematology, 45, 533-540. doi:10.1111/ijlh.14072. https://pubmed.ncbi.nlm.nih.gov/37058324/

6. Wilke, Anne C, Doebele, Carmen, Zindel, Alena, Zenz, Thorsten, Oellerich, Thomas. . SHMT2 inhibition disrupts the TCF3 transcriptional survival program in Burkitt lymphoma. In Blood, 139, 538-553. doi:10.1182/blood.2021012081. https://pubmed.ncbi.nlm.nih.gov/34624079/

7. Nie, Huiling, Yu, Yang, Zhou, Siqi, Wei, Bingbing, Qin, Xiaojian. . TCF3 as a multidimensional biomarker: oncogenicity, genomic alterations, and immune landscape in pan-cancer analysis. In Acta biochimica et biophysica Sinica, 57, 195-208. doi:10.3724/abbs.2024126. https://pubmed.ncbi.nlm.nih.gov/39205642/

8. Zeng, Wei, Jiang, Haixiao, Wang, Ying, Wang, Cunzu, Yu, Bo. 2022. TCF3 Induces DNMT1 Expression to Regulate Wnt Signaling Pathway in Glioma. In Neurotoxicity research, 40, 721-732. doi:10.1007/s12640-022-00510-w. https://pubmed.ncbi.nlm.nih.gov/35446002/

9. Wei, Xiao-Wei, Liu, Xue-Qing, Zhang, Yu-Chen, Lin, Yi, Tian, Fu-Ju. 2022. TCF3 regulates human endometrial stromal cell proliferation and migration in RPL. In Reproduction (Cambridge, England), 163, 281-291. doi:10.1530/REP-21-0463. https://pubmed.ncbi.nlm.nih.gov/35239510/