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Gene Review

KLF1  -  Kruppel-like factor 1 (erythroid)

Homo sapiens

Synonyms: CDAN4, EKLF, Erythroid krueppel-like transcription factor, HBFQTL6, INLU, ...
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Disease relevance of KLF1

  • We also propose that absence of AHSP in EKLF-null red cells exacerbates the toxicity of free alpha-globin chains, which exist because of the defect in beta-globin gene activation [1].
  • The DNA-binding domains (DBDs) of several zinc finger proteins, including EKLF, interact directly with SWI/SNF to generate DNase I hypersensitivity within the chromatin-assembled beta-globin promoter [2].
  • Availability of human EKLF will enable initiation of studies to molecularly assess whether it is functionally compromised in those cases of beta-thalassemia that contain a normal beta-globin gene locus [3].
  • Furthermore, the shear stress response region of the KLF2 promoter was specifically immunoprecipitated by antibodies against acetylated histones H3 and H4 in shear-stressed but not static hemangioendothelioma cells [4].
  • Northern blot analysis was used to study RNA expression in human colon cancer RKO cells engineered to overexpress KLF4 [5].

High impact information on KLF1

  • Erythroid Krüppel-like factor (EKLF) is necessary for stage-specific expression of the human beta-globin gene [6].
  • A SWI/SNF-related chromatin remodeling complex, E-RC1, is required for tissue-specific transcriptional regulation by EKLF in vitro [6].
  • EKLF contains three zinc-fingers homologous to those found in the Krüppel family of transcription factors [7].
  • Heterozygous EKLF+/- mice show that the reporter gene is expressed in a developmentally specific manner in all types of erythroblasts in the fetal liver and adult bone marrow [7].
  • We conclude that the transcription factor EKLF is essential for the final steps of definitive erythropoiesis in fetal liver [7].

Biological context of KLF1


Anatomical context of KLF1


Associations of KLF1 with chemical compounds

  • First, in vivo analyses implicate serine/threonine kinases as important players in the terminal differentiation of MEL cells, and demonstrate that EKLF is phosphorylated at serine and threonine residues within its transactivation region [15].
  • First, green fluorescent protein or pyruvate kinase was fused to EKLF domains, and localization was monitored and quantitated by confocal microscopy [16].
  • EKLF/KLF-1 is a 358-amino acid nuclear protein with an amino-terminal proline-rich domain and a carboxyl-terminal DNA binding domain [17].
  • EKLF/KLF-1 containing histidine to alanine mutations that disrupt the structure of all three fingers retains appropriate nuclear localization, indicating that neither the tertiary structure of the zinc fingers nor specific DNA binding are necessary for nuclear localization [17].
  • Cells were cotransfected with TR and/or KLF4 expression vectors and treated+/-100 nmol/L thyroid hormone (T3) [18].

Physical interactions of KLF1

  • Remodeling is achieved with only the BRG1-BAF155 minimal complex and the EKLF zinc finger DBD, whereas transcription requires, in addition, an activation domain [2].

Regulatory relationships of KLF1

  • Our results further indicate that in hematopoietic progenitors, EKLF influences chromatin organization at the human beta-globin locus and is instrumental for human beta-gene potentiation [19].

Other interactions of KLF1

  • Under our conditions, the transcripts encoding KLF1 and KLF9 were never detected [20].
  • Initially, 21 human proteins that have close sequence similarity to EKLF/KLF1, a known regulator of the human beta-globin gene, were identified [21].
  • Competition between Sp1 and a Krüppel-like factor for GC-rich sites has been previously reported, but this is the first description of an elaborate tripartite cooperation of two Krüppel-like factors and CREB as a key step in such a competition [22].
  • The first 47 amino acids of the acidic region are nearly identical to the amino-terminal portion of another Krüppel-like factor, the so-called core promoter-binding protein (CPBP) or Zf9 [23].
  • The core promoter of RH50 gene was located within 68bp length from the translation start position, which included an inverse GATA motif, although obvious motifs for Sp1 or erythroid Krüppel-like factor were lacking [24].

Analytical, diagnostic and therapeutic context of KLF1


  1. Genomic organisation and regulation of murine alpha haemoglobin stabilising protein by erythroid Kruppel-like factor. Keys, J.R., Tallack, M.R., Hodge, D.J., Cridland, S.O., David, R., Perkins, A.C. Br. J. Haematol. (2007) [Pubmed]
  2. Functional selectivity of recombinant mammalian SWI/SNF subunits. Kadam, S., McAlpine, G.S., Phelan, M.L., Kingston, R.E., Jones, K.A., Emerson, B.M. Genes Dev. (2000) [Pubmed]
  3. Isolation, genomic structure, and expression of human erythroid Krüppel-like factor (EKLF). Bieker, J.J. DNA Cell Biol. (1996) [Pubmed]
  4. Induction of KLF2 by fluid shear stress requires a novel promoter element activated by a phosphatidylinositol 3-kinase-dependent chromatin-remodeling pathway. Huddleson, J.P., Ahmad, N., Srinivasan, S., Lingrel, J.B. J. Biol. Chem. (2005) [Pubmed]
  5. Enterocyte differentiation marker intestinal alkaline phosphatase is a target gene of the gut-enriched Kruppel-like factor. Hinnebusch, B.F., Siddique, A., Henderson, J.W., Malo, M.S., Zhang, W., Athaide, C.P., Abedrapo, M.A., Chen, X., Yang, V.W., Hodin, R.A. Am. J. Physiol. Gastrointest. Liver Physiol. (2004) [Pubmed]
  6. A SWI/SNF-related chromatin remodeling complex, E-RC1, is required for tissue-specific transcriptional regulation by EKLF in vitro. Armstrong, J.A., Bieker, J.J., Emerson, B.M. Cell (1998) [Pubmed]
  7. Defective haematopoiesis in fetal liver resulting from inactivation of the EKLF gene. Nuez, B., Michalovich, D., Bygrave, A., Ploemacher, R., Grosveld, F. Nature (1995) [Pubmed]
  8. The Krüppel-like factor KLF2 inhibits peroxisome proliferator-activated receptor-gamma expression and adipogenesis. Banerjee, S.S., Feinberg, M.W., Watanabe, M., Gray, S., Haspel, R.L., Denkinger, D.J., Kawahara, R., Hauner, H., Jain, M.K. J. Biol. Chem. (2003) [Pubmed]
  9. Vascular implications of the Krüppel-like family of transcription factors. Suzuki, T., Aizawa, K., Matsumura, T., Nagai, R. Arterioscler. Thromb. Vasc. Biol. (2005) [Pubmed]
  10. Lipid defect underlies selective skin barrier impairment of an epidermal-specific deletion of Gata-3. de Guzman Strong, C., Wertz, P.W., Wang, C., Yang, F., Meltzer, P.S., Andl, T., Millar, S.E., Ho, I.C., Pai, S.Y., Segre, J.A. J. Cell Biol. (2006) [Pubmed]
  11. KLF2 Is a novel transcriptional regulator of endothelial proinflammatory activation. SenBanerjee, S., Lin, Z., Atkins, G.B., Greif, D.M., Rao, R.M., Kumar, A., Feinberg, M.W., Chen, Z., Simon, D.I., Luscinskas, F.W., Michel, T.M., Gimbrone, M.A., García-Cardeña, G., Jain, M.K. J. Exp. Med. (2004) [Pubmed]
  12. Alterations in expression and chromatin configuration of the alpha hemoglobin-stabilizing protein gene in erythroid Kruppel-like factor-deficient mice. Pilon, A.M., Nilson, D.G., Zhou, D., Sangerman, J., Townes, T.M., Bodine, D.M., Gallagher, P.G. Mol. Cell. Biol. (2006) [Pubmed]
  13. Activation and repression of interleukin-12 p40 transcription by erythroid Kruppel-like factor in macrophages. Luo, Q., Ma, X., Wahl, S.M., Bieker, J.J., Crossley, M., Montaner, L.J. J. Biol. Chem. (2004) [Pubmed]
  14. The human erythroid-specific transcription factor EKLF localizes to chromosome 19p13.12-p13.13. van Ree, J.H., Roskrow, M.A., Becher, A.M., McNall, R., Valentine, V.A., Jane, S.M., Cunningham, J.M. Genomics (1997) [Pubmed]
  15. Regulation of erythroid Krüppel-like factor (EKLF) transcriptional activity by phosphorylation of a protein kinase casein kinase II site within its interaction domain. Ouyang, L., Chen, X., Bieker, J.J. J. Biol. Chem. (1998) [Pubmed]
  16. Krüppel-like zinc fingers bind to nuclear import proteins and are required for efficient nuclear localization of erythroid Krüppel-like factor. Quadrini, K.J., Bieker, J.J. J. Biol. Chem. (2002) [Pubmed]
  17. Basic residues within the Kruppel zinc finger DNA binding domains are the critical nuclear localization determinants of EKLF/KLF-1. Pandya, K., Townes, T.M. J. Biol. Chem. (2002) [Pubmed]
  18. Convergence of the thyroid hormone and gut-enriched Krüppel-like factor pathways in the context of enterocyte differentiation. Siddique, A., Malo, M.S., Ocuin, L.M., Hinnebusch, B.F., Abedrapo, M.A., Henderson, J.W., Zhang, W., Mozumder, M., Yang, V.W., Hodin, R.A. J. Gastrointest. Surg. (2003) [Pubmed]
  19. Lineage-specific activators affect beta-globin locus chromatin in multipotent hematopoietic progenitors. Bottardi, S., Ross, J., Pierre-Charles, N., Blank, V., Milot, E. EMBO J. (2006) [Pubmed]
  20. Cell and tissue specific expression of human Krüppel-like transcription factors in human ocular surface. Chiambaretta, F., De Graeve, F., Turet, G., Marceau, G., Gain, P., Dastugue, B., Rigal, D., Sapin, V. Mol. Vis. (2004) [Pubmed]
  21. A functional screen for Krüppel-like factors that regulate the human gamma-globin gene through the CACCC promoter element. Zhang, P., Basu, P., Redmond, L.C., Morris, P.E., Rupon, J.W., Ginder, G.D., Lloyd, J.A. Blood Cells Mol. Dis. (2005) [Pubmed]
  22. An interplay of Sp1, GKLF and CREB-2 controls human Pre-alpha-Inhibitor gene (ITIH3) transcription. Ruminy, P., Rouet, P., Salier, J.P. Gene (2003) [Pubmed]
  23. Cloning the cDNA for a new human zinc finger protein defines a group of closely related Krüppel-like transcription factors. Matsumoto, N., Laub, F., Aldabe, R., Zhang, W., Ramirez, F., Yoshida, T., Terada, M. J. Biol. Chem. (1998) [Pubmed]
  24. Identification of 5' flanking sequence of RH50 gene and the core region for erythroid-specific expression. Iwamoto, S., Omi, T., Yamasaki, M., Okuda, H., Kawano, M., Kajii, E. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  25. Downregulation of GATA-1 expression during phorbol myristate acetate-induced megakaryocytic differentiation of human erythroleukemia cells. Dai, W., Murphy, M.J. Blood (1993) [Pubmed]
  26. Sp transcription factor family and its role in cancer. Safe, S., Abdelrahim, M. Eur. J. Cancer (2005) [Pubmed]
  27. Thalassaemia-like carriers not linked to the beta-globin gene cluster. Faà, V., Meloni, A., Moi, L., Ibba, G., Travi, M., Vitucci, A., Cao, A., Rosatelli, M.C. Br. J. Haematol. (2006) [Pubmed]
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