Disease relevance of Klf6

• Induction of Zf9 in the kidney following early ischemia/reperfusion [1].

High impact information on Klf6

• Collectively, these findings implicate Klf6 in ES-cell differentiation and hematopoiesis [2].
• We have previously established that Klf6 is expressed in neuronal tissue, hindgut, heart, lung, kidney, and limb buds during midgestation [2].
• To further analyze this phenotype, we generated Klf6-/- embryonic stem (ES) cells by homologous recombination, and compared their capacity to differentiate into the hematopoietic lineage with that of either Klf6+/- or Klf6+/+ ES cells [2].
• Krüppel-like factor 6 (KLF6) is a member of a growing family of transcription factors that share a common 3 C2H2 zinc finger DNA binding domain and have broad activity in regulating proliferation and development [2].
• Developmental regulation of yolk sac hematopoiesis by Kruppel-like factor 6 [2].

Biological context of Klf6

• Klf6 is a zinc finger protein expressed in a cell-specific manner during kidney development [3].
• Relative quantitative reverse transcription (RT)-PCR was performed to measure the KLF6 transcript level in eyes enucleated at embryonic stages, and the corneas and lenses isolated at postnatal stages [4].
• In cultured human proximal tubule cells, induction of ischemia by partial adenosine triphosphate (ATP) depletion resulted in a rapid up-regulation of both Zf9 and of TGF-beta1 proteins [1].
• Our data demonstrate that CPBP transcript is enriched in the trophoblastic tissue and strongly suggest that its encoded polypeptide regulates target genes involved in placental development and pregnancy maintenance [5].
• The FM2 enhancer appears to be unique to rodent; however, the FM enhancer region is deeply conserved in gnathostomes [6].

Anatomical context of Klf6

• Thereafter, Klf6 was expressed in the ureteric bud and its branches and in the collecting ducts, whereas it was not expressed in tubular structures that derive from the metanephric mesenchyme [3].
• In situ hybridization experiments using mouse embryos showed that during kidney development, Klf6 was expressed selectively in the Wolffian duct and in its derivatives [3].
• RESULTS: Staining for the KLF6 protein was observed at E10.5 in the lens pit and at E12.5 in the ectoderm, the mesenchyme, and the lens epithelium [4].
• Nuclear staining for KLF6 protein was evident at E15.5 in the corneal epithelium and the stroma [4].
• Studies of mutants lacking FM or FM2 enhancer demonstrated that these enhancers indeed regulate Otx2 expression in forebrain and midbrain [6].

Associations of Klf6 with chemical compounds

• Transcript of KLF6 was detected by in situ hybridization with digoxigenin-labeled RNA probes [4].

Regulatory relationships of Klf6

• TGF-beta1 protein was also up-regulated in a pattern parallel to that of Zf9 [1].

Analytical, diagnostic and therapeutic context of Klf6

• Northern blot analyses showed that Klf6 was already expressed in 11.5-d postconception mouse embryos and that its expression persisted after birth [3].
• Chromatin immunoprecipitation assay analysis revealed that the endogenous KLF-6/Zf9 binds the BS5-B elements that contain the CACCC motif, which is a consensus recognition sequence for other proteins in the KLF family [7].
• Western blot analysis indicated that c-Jun (an AP-1 protein), Kruppel-like factor 6 (KFL6), and inducible nitric oxide synthase (iNOS) were upregulated sequentially in that order [8].

1. Induction of Zf9 in the kidney following early ischemia/reperfusion. Tarabishi, R., Zahedi, K., Mishra, J., Ma, Q., Kelly, C., Tehrani, K., Devarajan, P. Kidney Int. (2005)
2. Developmental regulation of yolk sac hematopoiesis by Kruppel-like factor 6. Matsumoto, N., Kubo, A., Liu, H., Akita, K., Laub, F., Ramirez, F., Keller, G., Friedman, S.L. Blood (2006)
3. Klf6 is a zinc finger protein expressed in a cell-specific manner during kidney development. Fischer, E.A., Verpont, M.C., Garrett-Sinha, L.A., Ronco, P.M., Rossert, J.A. J. Am. Soc. Nephrol. (2001)
4. Developmentally regulated expression of KLF6 in the mouse cornea and lens. Nakamura, H., Chiambaretta, F., Sugar, J., Sapin, V., Yue, B.Y. Invest. Ophthalmol. Vis. Sci. (2004)
5. The Krüppel-like core promoter binding protein gene is primarily expressed in placenta during mouse development. Slavin, D., Sapin, V., López-Diaz, F., Jacquemin, P., Koritschoner, N., Dastugue, B., Davidson, I., Chatton, B., Bocco, J.L. Biol. Reprod. (1999)
6. Regulation of Otx2 expression and its functions in mouse forebrain and midbrain. Kurokawa, D., Kiyonari, H., Nakayama, R., Kimura-Yoshida, C., Matsuo, I., Aizawa, S. Development (2004)
7. The Kruppel-like factor Zf9 and proteins in the Sp1 family regulate the expression of HSP47, a collagen-specific molecular chaperone. Yasuda, K., Hirayoshi, K., Hirata, H., Kubota, H., Hosokawa, N., Nagata, K. J. Biol. Chem. (2002)
8. Geldanamycin treatment inhibits hemorrhage-induced increases in KLF6 and iNOS expression in unresuscitated mouse organs: role of inducible HSP70. Kiang, J.G., Bowman, P.D., Wu, B.W., Hampton, N., Kiang, A.G., Zhao, B., Juang, Y.T., Atkins, J.L., Tsokos, G.C. J. Appl. Physiol. (2004)