Alternative titles; symbols
HGNC Approved Gene Symbol: FOXN3
Cytogenetic location: 14q31.3-q32.11 Genomic coordinates (GRCh38): 14:89,156,177-89,619,165 (from NCBI)
Eukaryotic cells have DNA damage-inducible cell cycle arrests, or checkpoints, at G1 and G2. By screening a human glioblastoma cDNA library for cDNAs that could suppress S. cerevisiae checkpoint mutations, Pati et al. (1997) isolated a cDNA encoding FOXN3, which they called CHES1. The predicted 490-amino acid CHES1 protein is a member of the forkhead family of transcription factors (see 602341).
By in situ hybridization, Tribioli et al. (2002) showed that Ches1, which they called Foxn2, was not expressed in mouse embryos prior to embryonic day-9.5 (E9.5), and that earliest expression began in late E9.5 embryos. In postgastrulation mouse embryos, Ches1 was expressed in multiple tissues that served as important signaling centers, as well as in end-stage differentiated cell types that arose from different germ layers of developing embryos.
Pati et al. (1997) found that human CHES1 could suppress the Mec1 checkpoint mutation in yeast. Analysis of CHES1 activity suggested that it suppressed Mec1 and other DNA damage-activated checkpoint mutations in yeast by activating a Mec1-independent checkpoint pathway.
Scott and Plon (2005) showed that the C-terminal domain of FOXN3 repressed transcription of a reporter gene following transfection into several human cell lines. Yeast 2-hybrid analysis of a fetal brain cDNA library revealed that the FOXN3 C-terminal domain interacted with SKIIP (603055), a transcriptional coregulator that associates with repressor complexes. Coimmunoprecipitation analysis of epitope-tagged proteins confirmed the interaction in HeLa cells. Domain analysis revealed that the extreme C terminus of SKIIP interacted with the C-terminal domain of FOXN3.
By linkage to known markers, Pati et al. (1997) mapped the CHES1 gene to chromosome 14q24.3-q31.
Pati, D., Keller, C., Groudine, M., Plon, S. E. Reconstitution of a MEC1-independent checkpoint in yeast by expression of a novel human fork head cDNA. Molec. Cell. Biol. 17: 3037-3046, 1997. [PubMed: 9154802] [Full Text: https://doi.org/10.1128/MCB.17.6.3037]
Scott, K. L., Plon, S. E. CHES1/FOXN3 interacts with Ski-interacting protein and acts as a transcriptional repressor. Gene 359: 119-126, 2005. [PubMed: 16102918] [Full Text: https://doi.org/10.1016/j.gene.2005.06.014]
Tribioli, C., Robledo, R. F., Lufkin, T. The murine fork head gene Foxn2 is expressed in craniofacial, limb, CNS and somitic tissues during embryogenesis. Mech. Dev. 118: 161-163, 2002. [PubMed: 12351180] [Full Text: https://doi.org/10.1016/s0925-4773(02)00220-4]