Alternative titles; symbols
HGNC Approved Gene Symbol: FOXD4
Cytogenetic location: 9p24.3 Genomic coordinates (GRCh38): 9:116,231-118,417 (from NCBI)
Highly conserved winged-helix transcription factors, such as FOXD4, regulate embryonal development and tissue differentiation (Freyaldenhoven et al., 2002).
Forkhead genes are transcription factors distinguished by a characteristic 100-amino acid motif that was originally identified in Drosophila (see 164874). Pierrou et al. (1994) identified 7 human genes containing forkhead domains, including FREAC5. Northern blot analysis revealed that FREAC5 was expressed as a 4.0-kb mRNA in most tissues, principally in heart and skeletal muscle.
Fan et al. (2002) stated that the FOXD4 protein contains 439 amino acids and has a central forkhead domain.
By RT-PCR analysis of leukemia cell lines and normal CD34 (142230)-positive human blood progenitor cells, followed by screening a human genomic phage library, Freyaldenhoven et al. (2002) cloned FOXD4 and FOXD4L4 (FOXD4L2; 611085), which they called FOXD4A and FOXD4B, respectively. The deduced 439-amino acid FOXD4A protein has an N-terminal acidic region, a central winged-helix DNA-binding domain, and a C-terminal proline- and alanine-rich region. The N- and C-terminal regions are predicted to function as transcriptional regulatory motifs. Northern blot analysis detected a 1.5-kb FOXD4A transcript in all 3 hematopoietic cell lines examined. RT-PCR detected highest FOXD4A expression in placenta and skeletal muscle, with weaker expression in lung, brain, kidney, heart, and liver, and no expression in pancreas. FOXD4A was expressed in all fetal tissues examined except brain.
Pierrou et al. (1994) determined the DNA binding specificity of FKHL9 through selection of high-affinity binding sites from random sequence oligonucleotides.
Fan et al. (2002) determined that FOXD4 is a single-exon gene, and they identified a TATA box in the promoter region.
Larsson et al. (1995) mapped the FKHL9 gene to the pericentromeric region of chromosome 9 by fluorescence in situ hybridization and somatic cell hybrid analysis.
By genomic sequence analysis, Fan et al. (2002) mapped the FOXD4 gene to chromosome 9pter. They mapped the mouse Foxd4 gene to chromosome 19B.
Fan, Y., Newman, T., Linardopoulou, E., Trask, B. J. Gene content and function of the ancestral chromosome fusion site in human chromosome 2q13-2q14.1 and paralogous regions. Genome Res. 12: 1663-1672, 2002. [PubMed: 12421752] [Full Text: https://doi.org/10.1101/gr.338402]
Freyaldenhoven, B. S., Fried, C., Wielckens, K. FOXD4a and FOXD4b, two new winged helix transcription factors, are expressed in human leukemia cell lines. Gene 294: 131-140, 2002. [PubMed: 12234674] [Full Text: https://doi.org/10.1016/s0378-1119(02)00702-3]
Larsson, C., Hellqvist, M., Pierrou, S., White, I., Enerback, S., Carlsson, P. Chromosomal localization of six human forkhead genes, freac-1 (FKHL5), -3 (FKHL7), -4 (FKHL8), -5 (FKHL9), -6 (FKHL10), and -8 (FKHL12). Genomics 30: 464-469, 1995. [PubMed: 8825632] [Full Text: https://doi.org/10.1006/geno.1995.1266]
Pierrou, S., Hellqvist, M., Samuelsson, L., Enerback, S., Carlsson, P. Cloning and characterization of seven human forkhead proteins: binding site specificity and DNA bending. EMBO J. 13: 5002-5012, 1994. [PubMed: 7957066] [Full Text: https://doi.org/10.1002/j.1460-2075.1994.tb06827.x]