Alternative titles; symbols
HGNC Approved Gene Symbol: FOXN2
Cytogenetic location: 2p16.3 Genomic coordinates (GRCh38): 2:48,313,659-48,379,295 (from NCBI)
FOXN2 belongs to class 2 of the forkhead box (FOX) family of transcription factors, members of which lack a basic region at the C-terminal end of the FOX domain (review by Katoh and Katoh, 2004).
A region of the human T-cell leukemia virus long terminal repeat located between -155 and -117 is important in the regulation of gene expression by the ETS family of transcription factors (164720, 164740). In an attempt to identify additional cellular transcription factors that bind to this portion of the LTR, Li et al. (1992) used expression cloning with oligonucleotides corresponding to this element. A 1,239-bp cDNA, which encoded a protein capable of binding to this purine-rich region, was isolated from a Jurkat cDNA library. This protein, which they designated human T-cell leukemia virus enhancer factor (HTLF), contained a domain with homology to the forkhead DNA-binding domain. They concluded that it is a unique cellular gene that may function in the transcriptional regulation of the human T-cell leukemia virus long terminal repeat.
In their review, Katoh and Katoh (2004) grouped FOX proteins into class 1, which have a C-terminal basic region within their FOX domain, and class 2, which lack the basic region. Members of FOX subfamily N, including FOXN2, belong to class 2.
By RT-PCR analysis, Jeong et al. (2021) showed that HOXC6 (142972) expression upregulated expression of microRNA-188-5p (MIR188-5p) in human cells, and that increased MIR188-5p downregulated FOXN2 expression at both the mRNA and protein levels. The FOXN2 transcript contains a putative MIR188-5p-binding site within its 3-prime UTR, and MIR188-5p suppressed FOXN2 transcriptional activity by targeting the binding site. By suppressing expression of FOXN2, MIR188-5p regulated migration of cancer cells.
By analysis of a panel of mouse-human somatic cell hybrids varying in human chromosome content and by radioactive in situ hybridization, Li et al. (1992) mapped the HTLF gene to chromosome 2p22-p16. The HTLF gene is distinct from another forkhead domain DNA-binding protein, ILF (147685), which is localized to chromosome 17q25. Since the ETS1 gene is located on 11q23 and since translocations between 2p22-p16 and 11q23 have been observed in leukemia, it is possible that fusions between portions of the ETS1 and HTLF genes are a mechanism of leukemogenesis.
Gross (2024) mapped the FOXN2 gene to chromosome 2p16.3 based on an alignment of the FOXN2 sequence (GenBank BC063305) with the genomic sequence (GRCh38).
Gross, M. B. Personal Communication. Baltimore, Md. 1/16/2024.
Jeong, S., Kim, S. A., Ahn, S. G. HOXC6-Mediated miR-188-5p Expression Induces Cell Migration through the Inhibition of the Tumor Suppressor FOXN2. Int. J. Molec. Sci. 23: 9, 2021. [PubMed: 35008435] [Full Text: https://doi.org/10.3390/ijms23010009]
Katoh, M., Katoh, M. Human FOX gene family (Review). Int. J. Oncol. 25: 1495-1500, 2004. [PubMed: 15492844]
Li, C., Lusis, A. J., Sparkes, R., Tran, S.-M., Gaynor, R. Characterization and chromosomal mapping of the gene encoding the cellular DNA binding protein HTLF. Genomics 13: 658-664, 1992. [PubMed: 1639393] [Full Text: https://doi.org/10.1016/0888-7543(92)90138-i]