Alternative titles; symbols
HGNC Approved Gene Symbol: KLF9
Cytogenetic location: 9q21.12 Genomic coordinates (GRCh38): 9:70,384,604-70,414,657 (from NCBI)
The GC box is a common regulatory DNA element of eukaryotic genes. The promoter region of rat CYP1A1 (108330) contains a single GC box within a basic transcriptional element (BTE) required for constitutive expression of the gene. By screening a liver library for the ability to bind BTE, Imataka et al. (1992) isolated rat cDNAs encoding Sp1 (189906) and a protein that they designated Bteb (BTE-binding protein). Sequence analysis revealed that, like Sp1, Bteb contains 3 consecutive zinc finger motifs. In transient transfection experiments both Bteb and Sp1 stimulated promoters with repeated GC boxes. However, the CYP1A1 promoter with only 1 GC box was activated by Sp1 and repressed by Bteb. Ohe et al. (1993) used a rat Bteb cDNA to screen a human placenta library and isolated cDNAs encoding BTEB1. The sequences of the predicted 244-amino acid rat and human proteins are 98% identical. Imataka et al. (1992) and Ohe et al. (1993) found that the mRNAs encoding Bteb and BTEB1 contain a GC-rich leader sequence in the 5-prime untranslated region that has the potential to form stem-loop structures and that may control translation.
Imhof et al. (1999) found that mouse Bteb1 is a strong activator of Ap2-alpha (107580) promoter activity. They also showed that Bteb1 and Klf12 (607531), an Ap2-alpha repressor, interact in a mutually exclusive manner with overlapping binding sites within the promoter region of Ap2-alpha.
Using microarray analysis, Good and Tangye (2007) showed that naive splenic B cells expressed higher levels of transcription factors KLF4 (602253), KLF9, and PZLF (ZBTB16; 176797) compared with memory B cells. Activation of naive B cells through CD40 (109535) and B-cell receptor downregulated expression of these cellular quiescence-associated transcription factors. Overexpression of KLF4, KLF9, and PZLF in memory B cells delayed their entry into cell division and proliferation. Good and Tangye (2007) concluded that memory B cells undergo a rewiring process that results in a significantly reduced activation threshold compared with naive B cells, allowing them to enter division more quickly, to differentiate into Ig-secreting plasma cells, and to more rapidly produce antibodies.
Kuniba et al. (2009) determined that the KLF9 gene contains 2 exons.
By analysis of a somatic cell hybrid panel and by fluorescence in situ hybridization, Ohe et al. (1993) mapped the BTEB1 gene to 9q13.
By genomic sequence analysis, Kuniba et al. (2009) mapped the KLF9 gene to chromosome 9q21.11.
Simmen et al. (2004) found that ablation of the Bteb1 gene in female mice resulted in uterine hypoplasia, reduced litter size, and increased incidence of neonatal deaths in offspring. The reduced litter size resulted from fewer numbers of implantation sites rather than a defect in ovulation. Progesterone responsiveness of several uterine genes was altered with the Bteb1 null mutation. The results suggested that Bteb1 is a functionally relevant progesterone receptor (607311)-interacting protein and that Bteb1 selectively modulates cellular process regulated by the progesterone receptor A isoform in the uterine stroma.
Good, K. L., Tangye, S. G. Decreased expression of Kruppel-like factors in memory B cells induces the rapid response typical of secondary antibody responses. Proc. Nat. Acad. Sci. 104: 13420-13425, 2007. [PubMed: 17673551] [Full Text: https://doi.org/10.1073/pnas.0703872104]
Imataka, H., Sogawa, K., Yasumoto, K., Kikuchi, Y., Sasano, K., Kobayashi, A., Hayami, M., Fujii-Kuriyama, Y. Two regulatory proteins that bind to the basic transcription element (BTE), a GC box sequence in the promoter region of the rat P-4501A1 gene. EMBO J. 11: 3663-3671, 1992. [PubMed: 1356762] [Full Text: https://doi.org/10.1002/j.1460-2075.1992.tb05451.x]
Imhof, A., Schuierer, M., Werner, O., Moser, M., Roth, C., Bauer, R., Buettner, R. Transcriptional regulation of the AP-2-alpha promoter by BTEB-1 and AP-2rep, a novel wt-1/egr-related zinc finger repressor. Molec. Cell. Biol. 19: 194-204, 1999. [PubMed: 9858544] [Full Text: https://doi.org/10.1128/MCB.19.1.194]
Kuniba, H., Yoshiura, K., Kondoh, T., Ohashi, H., Kurosawa, K., Tonoki, H., Nagai, T., Okamoto, N., Kato, M., Fukushima, Y., Kaname, T., Naritomi, K., Matsumoto, T., Moriuchi, H., Kishino, T., Kinoshita, A., Miyake, N., Matsumoto, N., Niikawa, N. Molecular karyotyping in 17 patients and mutation screening in 41 patients with Kabuki syndrome. J. Hum. Genet. 54: 304-309, 2009. [PubMed: 19343044] [Full Text: https://doi.org/10.1038/jhg.2009.30]
Ohe, N., Yamasaki, Y., Sogawa, K., Inazawa, J., Ariyama, T., Oshimura, M., Fujii-Kuriyama, Y. Chromosomal localization and cDNA sequence of human BTEB, a GC box binding protein. Somat. Cell Molec. Genet. 19: 499-503, 1993. [PubMed: 8291025] [Full Text: https://doi.org/10.1007/BF01233255]
Simmen, R. C. M., Eason, R. R., McQuown, J. R., Linz, A. L., Kang, T.-J., Chatman, L., Jr., Till, S. R., Fujii-Kuriyama, Y., Simmen, F. A., Oh, S. P. Subfertility, uterine hypoplasia, and partial progesterone resistance in mice lacking the Kruppel-like factor 9/basic transcription element-binding protein-1 (Bteb1) gene. J. Biol. Chem. 279: 29286-29294, 2004. [PubMed: 15117941] [Full Text: https://doi.org/10.1074/jbc.M403139200]