Alternative titles; symbols
HGNC Approved Gene Symbol: KLF13
Cytogenetic location: 15q13.3 Genomic coordinates (GRCh38) : 15:31,326,835-31,435,665 (from NCBI)
KLF13 belongs to a family of transcription factors that contain 3 classical zinc finger DNA-binding domains consisting of a zinc atom tetrahedrally coordinated by 2 cysteines and 2 histidines (C2H2 motif). These transcription factors bind to GC-rich sequences and related GT and CACCC boxes (Scohy et al., 2000).
Although many genes are induced early after T-cell activation, a few, like RANTES (187011), are induced at the T-cell differentiation stage. The A promoter region of the RANTES gene binds REL (e.g., RELA, 164014) as well as non-REL proteins. Using Southwestern blotting of nuclear extracts of activated peripheral blood lymphocytes (PBL) probed with oligonucleotides from the RANTES promoter A and B sites, Song et al. (1999) identified proteins detected only at late activation stages. By screening a day 5 activated PBL library with a 3-tandem A site probe, Song et al. (1999) obtained a cDNA encoding the KLF13 protein, which they termed RFLAT (RANTES factor of late-activated T lymphocytes). The deduced 228-amino acid protein contains 3 contiguous TFIIIA (GTF3A; 600860)-like C-terminal DNA-binding zinc finger motifs, which are 65 to 73% homologous to SP1 (189906), SP3 (601804), and BTEB (602902). Its N terminus, which is preceded by a stretch rich in basic amino acids, is rich in proline, serine, and alanine residues. SDS-PAGE and Western blot analysis indicated that KLF13 is expressed as a phosphorylated 38-kD protein. Northern blot analysis revealed ubiquitous expression of 7.5- and 5.0-kb transcripts, with greatest abundance in PBL and thymus. Immunofluorescence and Western blot analysis showed that KLF13 is localized in the nucleus.
Using degenerate PCR primers based on the sequence for KLF1 (600599), Asano et al. (2000) cloned a cDNA from fetal liver erythroid cells that encodes KLF13, which they termed FKLF2 based on its structural similarity to FKLF (TIEG2; 603301). By Northern blot analysis, they showed that KLF13 was expressed as 4.4- and 1.5-kb transcripts in the bone marrow and striated muscles but not in 12 other human tissues analyzed.
By searching for sequences related to the zinc finger DNA-binding domain of SP1, followed by screening a fetal mouse liver cDNA library, Scohy et al. (2000) cloned mouse Klf13. Like the human protein, mouse Klf13 encodes a deduced 288-amino acid protein. Mouse and human KLF13 share 98% amino acid identity through the zinc finger domains and 87% identity overall. Residues within each of the 3 zinc fingers that establish specific contacts with DNA are completely conserved in KLF13, suggesting that both mouse and human KLF13 recognize a classical GC box. Klf13 also contains an N-terminal region rich in proline and alanine. RT-PCR analysis revealed Klf13 expression in all mouse tissues examined, with lowest levels in testis and liver.
Gelshift binding analysis by Song et al. (1999) demonstrated that KLF13 binds to the A and A/B RANTES promoter binding sites, but not the B site alone, and that NFKB (164011) also binds to these sites. Northern and Western blot analysis demonstrated that while KLF13 mRNA is detectable at constant steady state levels in resting and activated T cells, KLF13 protein appears only late after activation. Luciferase reporter assays showed that KLF13 can transactivate the RANTES gene; whereas KLF13 is the dominant transactivator of RANTES in T-cells, RELA is the dominant transactivator in fibroblasts.
Luciferase reporter assays by Asano et al. (2000) showed that KLF13 activates predominantly the gamma- (HBG1; 142200) and, to a lesser degree, the epsilon- (HBE1; 142100) and beta- (HBB; 141900) globin gene promoters. They found that KLF13 is involved in activation of transcription of a wide variety of genes in the cells of erythroid lineage, including GATA1 (305371), glycophorin B (617923), ferrochelatase (612386), porphobilinogen deaminase (HMBS; 609806), and 5-aminolevulinate synthase (125290).
Scott (2000) mapped the KLF13 gene to chromosome 15 based on sequence similarity between the KLF13 sequence (GenBank AF150628) and a chromosome 15 clone (GenBank AC009873). By somatic cell hybrid analysis, Scohy et al. (2000) mapped the KLF13 gene to chromosome 15. Suske et al. (2005) stated that the human KLF13 gene maps to chromosome 15q13.2, and the mouse Klf13 gene to chromosome 7C.
Asano, H., Li, X. S., Stamatoyannopoulos, G. FKLF-2: a novel Kruppel-like transcriptional factor that activates globin and other erythroid lineage genes. Blood 95: 3578-3584, 2000. [PubMed: 10828046]
Scohy, S., Gabant, P., Van Reeth, T., Hertveldt, V., Dreze, P.-L., Van Vooren, P., Riviere, M., Szpirer, J., Szpiper, C. Identification of KLF13 and KLF14 (SP6), novel members of the SP/XKLF transcription factor family. Genomics 70: 93-101, 2000. [PubMed: 11087666] [Full Text: https://doi.org/10.1006/geno.2000.6362]
Scott, A. F. Personal Communication. Baltimore, Md. 9/25/2000.
Song, A., Chen, Y. F., Thamatrakoln, K., Storm, T. A., Krensky, A. M. RFLAT-1: a new zinc finger transcription factor that activates RANTES gene expression in T lymphocytes. Immunity 10: 93-103, 1999. [PubMed: 10023774] [Full Text: https://doi.org/10.1016/s1074-7613(00)80010-2]
Suske, G., Bruford, E., Philipsen, S. Mammalian SP/KLF transcription factors: bring in the family. Genomics 85: 551-556, 2005. [PubMed: 15820306] [Full Text: https://doi.org/10.1016/j.ygeno.2005.01.005]