Alternative titles; symbols
HGNC Approved Gene Symbol: KLF14
Cytogenetic location: 7q32.2 Genomic coordinates (GRCh38): 7:130,730,697-130,734,207 (from NCBI)
KLF14 is a transcriptional repressor that limits PLK4 (605031)-directed centrosome amplification (Fan et al., 2015).
Suske et al. (2005) stated that the human and mouse KLF14 proteins contain 323 and 325 amino acids, respectively. Both have a characteristic zinc finger domain, but lack the N-terminal buttonhead box found in related SP transcription factors.
Using RT-PCR, Parker-Katiraee et al. (2007) found that KLF14 was expressed at low levels in many mouse and human tissues, with higher expression in fetal tissues and placenta than in adult tissues. It was not expressed in liver or lymphoblasts. KLF14 was monoallelically expressed from the maternal chromosome in all mouse and human embryonic tissues examined, but imprinting was not associated with the expected molecular signatures, such as DNA methylation.
Parker-Katiraee et al. (2007) determined that KLF14 is an intronless gene.
Suske et al. (2005) stated that the human KLF14 gene maps to chromosome 7q32.2, and the mouse Klf14 gene to chromosome 6A3.
By database analysis, Fan et al. (2015) found that KLF14 mRNA expression was significantly reduced in various human cancers and that it was negatively correlated with PLK4 expression. Database and reporter gene analyses identified KLF14 as a transcriptional repressor of PLK4 that inhibited PLK4-directed centriole duplication.
Small et al. (2011) showed that the lipid phenotype-associated cis-acting expression quantitative trait locus (eQTL), represented by rs4731702, of the maternally expressed transcription factor KLF14 is a master trans regulator of adipose gene expression. Expression levels of genes regulated by this trans-eQTL were highly correlated with concurrently measured metabolic traits, and a subset of the trans-regulated genes harbored variants directly associated with metabolic phenotypes.
Fan et al. (2015) found that Klf14 -/- mice were viable with no obvious abnormalities in body weight or serum lipids. However, loss of Klf14 led to spontaneous tumorigenesis in adult mice. Analysis with Klf14 -/- embryonic fibroblasts revealed that loss of Klf14 resulted in chromosome instability and caused centrosome amplification, thereby promoting tumorigenesis. Moreover, loss of Klf14 promoted azoxymethane- and dextran sulfate sodium-induced colon tumorigenesis in mice. Ectopic KLF14 expression in HeLa cells resulted in mitotic catastrophe, leading to cell death associated with Plk4 reduction.
The KLF14 gene on chromosome 7q32.2 should not be confused with the SP6 gene (608613) on chromosome 17q21.32, which has been referred to as KLF14 in the literature.
Fan, G., Sun, L., Shan, P., Zhang, X., Huan, J., Zhang, X., Li, D., Wang, T., Wei, T., Zhang, X., Gu, X., Yao, L., Xuan, Y., Hou, Z., Cui, Y., Cao, L., Li, X., Zhang, S., Wang, C. Loss of KLF14 triggers centrosome amplification and tumorigenesis. Nature Commun. 6: 8450, 2015. [PubMed: 26439168] [Full Text: https://doi.org/10.1038/ncomms9450]
Parker-Katiraee, L., Carson, A. R., Yamada, T., Arnaud, P., Feil, R., Abu-Amero, S. N., Moore, G. E., Kaneda, M., Perry, G. H., Stone, A. C., Lee, C., Meguro-Horike, M., Sasaki, H., Kobayashi, K., Nakabayashi, K., Scherer, S. W. Identification of the imprinted KLF14 transcription factor undergoing human-specific accelerated evolution. PLoS Genet. 3: e65, 2007. Note: Electronic Article. [PubMed: 17480121] [Full Text: https://doi.org/10.1371/journal.pgen.0030065]
Small, K. S., Hedman, A. K., Grundberg, E., Nica, A. C., Thorleifsson, G., Kong, A., Thorsteindottir, U., Shin, S.-Y., Richards, H. B., GIANT Consortium, MAGIC Investigators, DIAGRAM Consortium, and 9 others. Identification of an imprinted master trans regulator at the KLF14 locus related to multiple metabolic phenotypes. Nature Genet. 43: 561-564, 2011. Note: Erratum: Nature Genet. 43: 1040 only, 2011. [PubMed: 21572415] [Full Text: https://doi.org/10.1038/ng.833]
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]